On May 19, 2021 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported the upcoming presentation of updated results from the Company’s priority development pathways in head and neck cancer (head and neck squamous cell carcinoma; HNSCC) and in immunotherapy for advanced cancers at the 2021 Annual Meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Nanobiotix, MAY 19, 2021, View Source [SID1234580315]). The Company will also present a poster with long-term safety analysis from its pivotal phase II/III study in soft tissue sarcoma.

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"The data we will present at ASCO (Free ASCO Whitepaper) provide further support for the paradigm-shifting potential of NBTXR3 as a foundational solid tumor-agnostic and combination-agnostic cancer therapeutic," said Laurent Levy, co-founder and chief executive officer of Nanobiotix. "We are excited to present both long-term safety data from our phase III soft tissue sarcoma study, along with updated safety and efficacy data from our second single-agent registration pathway in head and neck cancer. Moreover, we are particularly eager to present a growing body of data suggesting that after activation by radiotherapy, NBTXR3 may prime an immune response that could enhance the efficacy of immune checkpoint inhibitors as a first-line therapy, overcome resistance for refractory patients, and meaningfully expand the tumor types that respond to the class by transforming cold tumors into hot tumors."

Local Control as a Single-Agent for Patients with Head and Neck Cancer

Abstract #6051: Phase I Dose Expansion Study of Functionalized Hafnium Oxide Nanoparticles (NBTXR3) in Cisplatin-Ineligible Locally Advanced HNSCC Patients

The number of elderly patients diagnosed with locally advanced HNSCC (LA-HNSCC) is increasing. While concurrent chemoradiation is the non-surgical standard of care, not all patients can tolerate platinum-based chemotherapy (e.g., cisplatin). The Nanobiotix phase I dose expansion study in patients with LA-HNSCC (Study 102) is evaluating a single dose of NBTXR3 at 22% of baseline tumor volume (the recommended phase II dose; RP2D). Primary endpoints of the study are objective response rate (ORR) and complete response rate (CRR) of the primary tumor. Study 102 is expected to recruit a total of 44 evaluable patients. To date, 52 total patients have been injected with NBTXR3 in the study overall, of which 40 have been evaluable.

Updated data presented at ASCO (Free ASCO Whitepaper) further support NBTXR3 administration, followed by activation with radiotherapy, as feasible and well-tolerated. Six (6) serious adverse events (SAEs) related to NBTXR3 were observed across five (5) patients. A total of ten (10) deaths related to adverse events were reported. Four (4) deaths related to radiotherapy were observed, along with one (1) death from sepsis that was investigator-assessed as possibly related to NBTXR3, radiotherapy, and cancer.

At a median follow up of 8.1 months, evaluable patients demonstrated a high primary tumor ORR of 82.5% and a 62.5% CRR. These results are consistent with those observed in the dose escalation part of the study and suggest durability of efficacy.

Nanobiotix plans to launch a pivotal phase III global registration trial evaluating NBTXR3 as a single-agent activated by radiotherapy for patients with LA-HNSCC in 2021.

Priming Immune Response and Immunotherapy Combination Across Oncology

Abstract #2590: A Phase I Study of NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy
Abstract #2591: Overcoming Resistance to Anti-PD-1 with Tumor-Agnostic NBTXR3: From Bench to Bedside

Cancer immunotherapies such as anti-PD-1 have shown promising clinical outcomes over the past two decades and are often used to treat advanced cancers once other therapies have reached the end of their effectiveness. However, across tumor indications, the significant majority of patients (80-85% according to published data) receive only a temporary benefit from anti-PD-1—or no benefit at all—as they either develop resistance to the therapy over time or are non-responsive to treatment altogether.

Previously reported data from the Company’s phase I immunotherapy study in advanced cancers (Study 1100) and its preclinical collaboration with The University of Texas MD Anderson Cancer Center support NBTXR3 activated by radiotherapy as a potential primer of immune response. These data suggest that when combined with anti-PD-1, NBTXR3 could contribute to tumor regression in patients with advanced and metastatic tumors regardless of the patient’s prior exposure to anti-PD-1.

Nanobiotix will provide an update on Study 1100 with additional patients and further follow up prior to the conference (abstract #2590). The Company will also present a compilation of preclinical and clinical data supporting NBTXR3 as a potentially tumor-agnostic, therapeutic combination-agnostic agent that could overcome resistance to immune checkpoint inhibitors and increase response rates across tumor indications (abstract #2591).

Local Control as a Single-Agent for Patients with Soft Tissue Sarcoma

Abstract #11544: Long-Term Evaluation of the Novel Radioenhancer NBTXR3 plus Radiotherapy in Patients with Locally Advanced Soft Tissue Sarcoma Treated in the Phase III Act.in.Sarc Trial

A long-term safety analysis following the Nanobiotix phase II/III pivotal study evaluating NBTXR3 as a single-agent activated by radiotherapy in patients with locally advanced soft tissue sarcoma (STS) did not observe a negative impact on patient quality of life and long-term morbidity. The long-term safety profile of NBTXR3, together with its efficacy data, further supported a favorable benefit-risk ratio for patients with STS. The analysis highlighted potential for future indications, including non-resectable sarcoma, pediatric tumors, and re-irradiation.

Nanobiotix Investor Event

Nanobiotix will host a virtual investor event featuring several key opinion leaders, including study investigators, after the ASCO (Free ASCO Whitepaper) Annual Meeting on Friday, June 11, 2021 at 8 am ET. The discussion will expand on the new immunotherapy results from Study 1100 that will be reported prior to ASCO (Free ASCO Whitepaper), providing additional detail and clinical perspective, following the ASCO (Free ASCO Whitepaper) presentation. Register here.

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About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and a phase III global registrational study is planned to launch in 2021. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the planned phase III study.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company-sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.

On May 19, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced publication of three abstracts on neratinib for the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held virtually from June 4-8, 2021 (Press release, Puma Biotechnology, MAY 19, 2021, View Source [SID1234580314]). Puma will present three posters with audio recordings, the corresponding abstracts of which are now live on the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting website. The full posters will be available on the Puma and ASCO (Free ASCO Whitepaper) websites at approximately 9:00 a.m. EDT on June 4, 2021.

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Poster Session: Breast Cancer—Local/Regional/Adjuvant

Abstract 540: Association between treatment duration and overall survival in early-stage HER2+ breast cancer patients receiving extended adjuvant therapy with neratinib in the ExteNET trial.
B Moy, M Takahashi, S Ohtani, E Chmielowska, N Yamamoto, B Coudert, F Xu, A Wong, A Chan
Abstract 536: Dose escalation for mitigating diarrhea: Ranked tolerability assessment of antidiarrheal regimens in patients receiving neratinib for early-stage breast cancer.
G Marx, AJ Chien, JA García-Sáenz, A Chan, M Ruiz-Borrego, CH Barcenas, M Thirlwell, M Trudeau, R Bose, D Egle, B Pistilli, J Wasserman, KA Cheong, D Semsek, C Singer, D Hunt, U Khambholja, F Xu, N Shah, A Brufsky
Poster Session: Lung Cancer—Non-Small Cell Metastatic

Abstract 9068: Neratinib efficacy in a subgroup of patients with EGFR exon 18-mutant non-small cell lung cancer (NSCLC) and central nervous system (CNS) involvement: findings from the SUMMIT basket trial.
JW Goldman, SV Ramírez, A Mahipal, JM Suga, LD Eli, AS Lalani, R Bryce, F Xu, N Shah, F Kabbinavar, V Boni, B Haley
The abstracts are available online at: asco.org/abstracts

On May 19, 2021 Arcus Biosciences, Inc. (NYSE:RCUS), an oncology-focused biopharmaceutical company working to create best-in-class cancer therapies, reported initial efficacy and safety data from one of the cohorts in ARC-6, a randomized Phase 1b/2 platform study, evaluating the novel combination of etrumadenant (dual adenosine A2a/A2b receptor antagonist) plus zimberelimab (anti-PD1 antibody) and docetaxel in people with taxane-naïve mCRPC who progressed following treatment with one or more new hormonal agents and were checkpoint inhibitor-naïve (Press release, Arcus Biosciences, MAY 19, 2021, View Source [SID1234580313]). In this Phase 1b cohort of the etrumadenant-based combination, a composite ORR (radiographic and/or PSA [prostate-specific antigen] response) of 41% and a PSA response of 35% were observed. The safety profile was consistent with the known profiles of each individual agent, and no significant additive toxicity was observed with the addition of etrumadenant. These data will be presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 4-8.

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"We are encouraged by these early data that indicate the etrumadenant-based combination is well tolerated and demonstrates promising clinical activity in people with advanced disease who progressed on prior treatments," said Bill Grossman, M.D., Ph.D., Chief Medical Officer of Arcus. "Based on these data, we have initiated enrollment into the randomized Phase 2 portion of this arm in the ARC-6 platform study, which compares the etrumadenant-based regimen to standard of care."

"Prostate tumors produce high levels of adenosine, which is believed to be immunosuppressive," said Sumit K. Subudhi, M.D., Ph.D., Department of Genitourinary Medical Oncology, Division of Cancer Medicine at the University of Texas, M.D. Anderson Cancer Center. "I am encouraged by the early evidence of clinical response and composite ORR of 41% observed in this study cohort, indicating adenosine receptor blockade with an etrumadenant-based combination may have a role in the treatment of prostate cancer."

ARC-6: A Phase 1b/2, Open-Label, Randomized Platform Study to Evaluate Efficacy and Safety of Etrumadenant (AB928)-Based Treatment Combinations in Patients with Metastatic Castrate-Resistant Prostate Cancer (Abstract 5039)

As of the data cut-off (DCO) of April 9, 2021, 17 people (n=17) had received the etrumadenant-based combination in this cohort of the Phase 1b portion of the study. Median time on treatment was 4.2 months (range: 2.1-8.3+ months), and 11 people remained on study treatment at time of DCO. For this cohort, all people had received prior systemic therapy but were taxane naive; most (13/17; 76%) had received ≥1 prior anti-androgen, and 11/17 people (65%) had received prior abiraterone.

Safety Analyses:

People in this cohort of the study were administered 150 mg of etrumadenant orally once daily plus 360 mg of zimberelimab and 75mg/m2 of docetaxel intravenously every three weeks.
All people experienced treatment emergent adverse events (TEAE), and the most common TEAEs were alopecia (53%), lymphocyte count decreases (53%) and fatigue (47%).
Grade 3 or 4 related TEAEs were reported for 6/17 (35%) people; all of these events were related to etrumadenant and may also be attributed to zimberelimab and/or docetaxel.
No treatment emergent serious adverse events (TESAEs) were considered related to etrumadenant.
Clinical Activity:

The composite ORR (radiographic and/or PSA response) was 41% (7/17) per the Prostate Cancer Working Group 3 (PCWG3) criteria.
Six people (35%) had a >50% decrease in PSA level, and seven people (41%) had non-response/non-progression.
All 11 people with RECIST measurable or non-measurable disease experienced clinical benefit (stable disease or better).
One unconfirmed complete response (CR) was observed in a person with only non-target disease remaining.
Two confirmed partial responses (PRs) were observed; one person with PR also had improvement in bone disease burden.
The safety and clinical activity data from this cohort of ARC-6 add to the emerging body of evidence that adenosine receptor blockade with an etrumadenant-based combination may have a role in the treatment of certain cancers. Based on these results, Arcus has initiated the randomized portion of this cohort which is evaluating this etrumadenant-based combination compared to docetaxel, the current standard of care for this setting.

Additional information about this poster presentation may be found on the Arcus website at Arcus Publications on June 4.

In addition to ARC-6, etrumadenant is currently being evaluated in three randomized Phase 2 studies:

ARC-7 is evaluating domvanalimab (anti-TIGIT antibody) plus zimberelimab vs. zimberelimab alone vs. domvanalimab plus zimberelimab and etrumadenant in first-line metastatic, PD-L1>50%, locally advanced or metastatic non-small cell lung cancer (NSCLC), with an interim analysis planned for this quarter.
ARC-4 is evaluating etrumadenant plus chemotherapy and zimberelimab vs. chemotherapy plus zimberelimab in second-line (2L) or third-line (3L) EGFR-positive NSCLC. Data from this study are expected in the second half of 2021.
ARC-9 is evaluating etrumadenant-based combinations in 2L and 3L metastatic colorectal cancer (mCRC). These data build on the results of ARC-3, a Phase 1/1b open-label study of etrumadenant plus chemotherapy in people with mCRC, which showed encouraging tolerability and efficacy in the 3L setting compared to standard of care. Data from this study are expected in the first half of 2022.
About Etrumadenant

Etrumadenant (AB928), the first dual A2a/A2b adenosine receptor antagonist in the clinic, is designed to maximally inhibit the adenosine-driven impairment of tumor-infiltrating lymphocytes (mainly CD8+ T cells and NK cells) and myeloid cells (dendritic cells, macrophages), mediated by A2aR and A2bR, respectively. A2bR is also upregulated by certain cancer cells, such as in prostate cancer and KRAS-mutated cancers. As a result, etrumadenant may uniquely block adenosine’s immunosuppressive and cancer cell-intrinsic effects. Developed specifically for the oncology setting, etrumadenant achieves high penetration of tumor tissue, robust potency in the presence of high adenosine concentrations, and minimal shift in potency from non-specific protein binding. Etrumadenant has demonstrated a favorable safety profile with a variety of combination regimens and exhibits pharmacokinetics / pharmacodynamics consistent with once-daily oral dosing. AB928 is currently being evaluated in several Phase 1b/2 studies across multiple indications.

On May 19, 2021 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported a trials in progress poster presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually from June 4-8, 2021 (Press release, Scholar Rock, MAY 19, 2021, View Source [SID1234580312]).

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The DRAGON Phase 1 proof-of-concept trial (NCT04291079) is evaluating SRK-181, a selective inhibitor of TGFβ1 activation, in patients with locally advanced or metastatic solid tumors that have shown primary resistance to checkpoint inhibitor therapies. Dose escalation is progressing in Part A of the trial and the Company expects to advance to the Part B dose expansion portion of the trial in mid-2021.

The trials in progress e-poster will provide an overview of the design of the DRAGON Phase 1 trial and highlight the biomarker analysis being implemented to support the trial. Details of the poster presentation are as follows:

Session: Developmental Therapeutics–Molecularly Targeted Agents and Tumor Biology
Title: "First-in-Human Phase 1 Trial (DRAGON) of SRK-181: A Potential First-in-Class Selective Latent TGFβ1 Inhibitor, Alone or in Combination with Anti-PD-(L)1 Treatment in Patients with Advanced Solid Tumors" (TPS3146)
Date and Time: Friday, June 4, 11:00 AM – 2:00 PM EDT; Poster sessions available on demand in meeting library beginning 9:00 AM EDT on June 4, 2021.
About SRK-181

SRK-181 is a selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity (1). Scholar Rock believes SRK-181, which specifically targets the latent TGFβ1 isoform, has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The efficacy and safety of SRK-181 have not been established. SRK-181 has not been approved for any use by the FDA nor any other regulatory agency.

(1) Martin et al., Sci. Transl. Med. 12: 25 March 2020

On May 19, 2021 AstraZeneca reported that it will present new data underscoring its ambition to redefine cancer care at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 4 to 8, 2021 (Press release, AstraZeneca, MAY 19, 2021, View Source [SID1234580311]).

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More than 100 abstracts will feature 21 approved and potential new medicines across the Company’s industry-leading oncology portfolio, with four abstracts selected as late-breakers, 12 oral presentations and one plenary presentation.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "Our data at ASCO (Free ASCO Whitepaper) this year show our unwavering resolve to revolutionize cancer care and strengthen our leading portfolio in lung and breast cancers as well as hematology. New results for LYNPARZA (olaparib) and IMFINZI (durvalumab) continue to validate our strategy of treating cancer early in settings with curative intent, and data for CALQUENCE deliver on our commitment to improve the patient experience by demonstrating efficacy with safe, tolerable medicines."

Cristian Massacesi, Senior Vice President, Head of Late-Stage Development, Oncology R&D said: "Over the past few years, the outlook for breast cancer patients with BRCA mutations has radically changed, and the OlympiA data at ASCO (Free ASCO Whitepaper) will represent another critical step forward. We have an opportunity to fundamentally change the prognosis for women with high-risk early disease and usher in a potential new standard of care in the adjuvant setting. Additionally, promising data in triple-negative breast cancer will challenge current treatment expectations and bring hope for new approaches in this aggressive form of the disease."

Redefining survival by treating cancer earlier
A plenary presentation of results from the OlympiA Phase III trial in early breast cancer will highlight the impact of LYNPARZA on the risk of disease recurrence versus placebo in the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. LYNPARZA is the first PARP inhibitor to demonstrate clinical benefit as an adjuvant treatment in early breast cancer. In February 2021, the trial’s Independent Data Monitoring Committee recommended moving to early primary analysis based on a planned interim analysis showing a sustainable and clinically relevant treatment effect in the primary endpoint of invasive disease-free survival.

Five-year overall survival data from the PACIFIC Phase III trial will continue to support the unprecedented and sustained survival benefits of IMFINZI for patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who have not progressed following concurrent chemoradiation therapy. These data represent the longest-ever survival reported in a Phase III trial of immunotherapy in this treatment setting.

Additionally, an oral presentation of Phase II data from the externally sponsored GeparNuevo trial conducted by the German Breast Group will show initial potential of IMFINZI to improve outcomes in patients with early triple-negative breast cancer (TNBC) when added to standard neoadjuvant chemotherapy.

Transforming the patient experience
Four-year follow-up data from the ELEVATE-TN trial will confirm the sustained clinical benefit of either CALQUENCE (acalabrutinib) monotherapy or CALQUENCE in combination with obinutuzumab, providing flexibility to tailor treatment for adults with treatment-naïve chronic lymphocytic leukemia (CLL).

In addition, an oral presentation of detailed results from the ELEVATE-RR Phase III trial will demonstrate significantly lower atrial fibrillation, fewer cardiac events and fewer discontinuations with CALQUENCE versus ibrutinib in adults with previously treated CLL at high risk for progression. ELEVATE-RR is the first head-to-head Phase III trial of two Bruton’s tyrosine kinase inhibitors (TKIs) in CLL, confirming the favorable benefit-risk profile of CALQUENCE for patients with CLL.

Updated data from DESTINY-Gastric01 and DESTINY-CRC01 will further support the potential role of ENHERTU (fam-trastuzumab deruxtecan-nxki) across HER2-targetable cancers. Additionally, data from a subgroup analysis of previously treated HER2-positive breast cancer patients with brain metastases in the DESTINY-Breast01 trial will reinforce the commitment to understanding the potential benefit of ENHERTU in hard-to-treat patient populations.

Initial results will be shared from the BEGONIA Phase Ib/II trial testing IMFINZI combinations in metastatic TNBC, including with ENHERTU. Also, data will be shared from a Phase II trial with ceralasertib, an ataxia telangiectasia and rad3-related (ATR) kinase inhibitor, in combination with IMFINZI showing that this combination demonstrated promising anti-tumor activity in melanoma patients for whom prior anti-PD1 treatment had failed.

Additional evidence will underscore the need for improved central nervous system control and the role of next-generation TKIs such as TAGRISSO (osimertinib) in the treatment of advanced epidermal growth factor (EGFR)-mutated NSCLC, as shown in the REFLECT retrospective real-world analysis of first- and second-generation TKIs.

Advancing an industry-leading clinical development program
In all, AstraZeneca will share 18 posters at ASCO (Free ASCO Whitepaper) describing trials-in-progress exploring novel medicines and combinations across multiple types and stages of cancer. These posters include:

Datopotamab deruxtecan (Dato-DXd) – the TROPION-Lung01 Phase III trial testing datopotamab deruxtecan in patients with previously treated metastatic NSCLC, and the BEGONIA trial testing IMFINZIin combination with datopotamab deruxtecan in metastatic TNBC
ENHERTU – trials testing ENHERTU alone or in various combinations, including: DESTINY-Breast07, DESTINY-PanTumor01, and DESTINY-CRC02
IMFINZI – the MATTERHORN Phase III trial of neoadjuvant-adjuvant IMFINZI and chemotherapy in resectable gastric and gastroesophageal junction cancer, and the BEGONIA Phase I/II trial testing IMFINZI in novel combinations for 1st-line treatment of patients with TNBC, including with ENHERTU and datopotamab deruxtecan.
CALQUENCE – the ESCALADE Phase III trial of CALQUENCE in combination with standard chemotherapy for patients age 65 and younger newly diagnosed with diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma
Camizestrant (AZD9833) – the SERENA-4 Phase III trial comparing camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), plus palbociclib, versus anastrozole plus palbociclib, in patients with estrogen receptor-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease
Adavosertib – the ADAGIO Phase II multicenter trial of the WEE1 inhibitor adavosertib as a treatment for recurrent or persistent uterine serous carcinoma, a highly aggressive form of endometrial cancer
Collaboration in the scientific community is critical to improving outcomes for patients. LYNPARZA is developed and commercialized in collaboration with Merck & Co., Inc. AstraZeneca is collaborating with Daiichi Sankyo Company, Limited (Daiichi Sankyo) to develop and commercialize ENHERTU and datopotamab deruxtecan globally.

Key AstraZeneca presentations during the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting1

Lead author

Abstract title

Presentation details2

Immuno-Oncology

Spigel, D

Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: An update from the PACIFIC trial.

Abstract #8511

Poster Discussion Session

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

June 4, 2021

Janjigian, Y

MATTERHORN: Efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer—A randomized, double-blind, placebo-controlled, phase 3 study.

Abstract #TPS4151

Poster Session

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

June 4, 2021

McCoon, P

T-cell receptor pharmacodynamics associated with survival and response to tremelimumab (T) in combination with durvalumab (D) in patients (pts) with unresectable hepatocellular carcinoma (uHCC).

Abstract #4087

Poster Session

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

June 4, 2021

Schmid, P

BEGONIA: Phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC)—Initial results from arm 1, d+paclitaxel (P), and arm 6, d+trastuzumab deruxtecan (T-DXd).

Abstract #1023

Poster Discussion Session

Breast Cancer—Metastatic

June 4, 2021

Schmid, P

BEGONIA: Phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first line metastatic triple-negative breast cancer (mTNBC): Addition of Arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062).

Abstract #TPS1105

Poster Session

Breast Cancer—Metastatic

June 4, 2021

Kwon, M

Phase II study of ceralasertib (AZD6738), in combination with durvalumab in patients with metastatic melanoma who have failed prior anti-PD-1 therapy.

Abstract #9514

Poster Discussion Session

Melanoma/Skin Cancers

June 4, 2021

Suárez, C

Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer.

Abstract #4511

Poster Discussion Session

Genitourinary Cancer—Kidney and Bladder

June 4, 2021

Tumor drivers and resistance

Janzic, U

Real-world outcomes and clinical characteristics of patients with brain metastases from EGFR mutated non-small cell lung cancer: Data from a large retrospective study (REFLECT).

Abstract #9086

Poster Session

Lung Cancer—Non-Small Cell Metastatic

June 4, 2021

Im, S-A

SERENA-4: A phase 3 comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease.

Abstract #TPS1101

Poster Session

Breast Cancer—Metastatic

June 4, 2021

Tada, H

Adjuvant gefitinib versus cisplatin/vinorelbine in Japanese patients with completely resected, EGFR-mutated, stage II-III non-small cell lung cancer (IMPACT, WJOG6410L): A randomized phase 3 trial.

Abstract #8501

Oral Abstract Session

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

June 6, 2021

Antibody drug conjugates

Yoh, K

A randomized, phase 3 study of datopotamab deruxtecan (Dato-DXd; DS-1062) versus docetaxel in previously treated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (TROPION-Lung01).

Abstract #TPS9127

Poster Session

Lung Cancer – Non-small Cell Metastatic

June 4, 2021

Andre, F

Trastuzumab deruxtecan (T-DXd) combinations in patients with HER2-positive advanced or metastatic breast cancer: A phase 1b/2, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast07).

Abstract #TPS1096

Poster Session

Breast Cancer—Metastatic

June 4, 2021

Li, BT

A phase 2, multicenter, open-label study evaluating trastuzumab deruxtecan (T-DXd) for the treatment of solid tumors harboring specific HER2-activating mutations (DESTINY-PanTumor01).

Abstract #TPS3162

Poster Session

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

June 4, 2021

Yoshino, T

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01).

Abstract #3505

Oral Abstract Session

Gastrointestinal Cancer—Colorectal and Anal

June 7, 2021

Raghav, K

Trastuzumab deruxtecan in patients with HER2-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC): A randomized, multicenter, phase 2 study (DESTINY-CRC02).

Abstract #TPS3620

Poster Session

Gastrointestinal Cancer—Colorectal and Anal

June 4, 2021

Jerusalem, G

Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: a subgroup analysis of the DESTINY-Breast01 trial.

Abstract #526

Poster Session

Breast Cancer— Local/Regional/Adjuvant

June 4, 2021

Yamaguchi, K

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY-Gastric01).

Abstract #4048

Poster Session

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

June 4, 2021

DNA damage response

Tutt, A

OlympiA: A phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high risk HER2-negative early breast cancer.

Abstract #LBA1

Plenary Session

June 6, 2021, 1:00pm EDT

Liu, JF

ADAGIO: A phase IIb, open-label, single-arm, multicenter study assessing the efficacy and safety of adavosertib (AZD1775) as treatment for recurrent or persistent uterine serous carcinoma.

Abstract #TPS5612

Poster Session

Gynecologic Cancer

June 4, 2021

Poveda, A

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

Abstract #5545

Poster Session

Gynecologic Cancer

June 4, 2021

Matthews, CA

Olaparib treatment (Tx) in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Overall survival (OS) results from the phase II LIGHT study.

Abstract #5515

Poster Discussion Session

Gynecologic Cancer

June 4, 2021

Pautier, P

Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial.

Abstract #5514

Poster Discussion Session

Gynecologic Cancer

June 4, 2021

Hematology

Byrd, J

First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia.

Abstract #7500

Oral Abstract Session

Hematologic Malignancies

June 7, 2021

Sharman, JP

Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Elevate-TN four-year follow up.

Abstract #7509

Poster Discussion Session

Hematologic Malignancies

June 4, 2021

Sehn, L

ESCALADE: A phase 3 study of acalabrutinib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for patients ≤65y with untreated non-germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL).

Abstract #TPS7572

Poster Session

Hematologic Malignancies

June 4, 2021

174 company-sponsored or supported abstracts will be presented at ASCO (Free ASCO Whitepaper) 2021.

2Beginning Friday,June 4, 2021 09:00 EDT oral presentations, poster discussions and poster sessions will be available on demand for 180 days including video and slide presentations and discussant commentary.

SELECT SAFETY INFORMATION for LYNPARZA (olaparib) tablets
LYNPARZA is associated with serious, potentially fatal risks, including myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), pneumonitis. Additionally, serious, potentially fatal risk of venous thromboembolic events has been reported with LYNPARZA in mCRPC. LYNPARZA can also cause fetal harm.

U.S. FDA-APPROVED INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation, and/or
genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm Ovarian Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm, HER2-Negative Metastatic Breast Cancer
For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

SELECT SAFETY INFORMATION FOR IMFINZI (durvalumab)
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. IMFINZI can cause severe or life-threatening infusion-related reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.

Advise women not to become pregnant or breastfeed during treatment with IMFINZI and for at least 3 months after the last dose.

In the PACIFIC trial, the most frequent serious adverse reactions reported in at least 2% of patients were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%).

The most common adverse reactions were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.

The safety and effectiveness of IMFINZI have not been established in pediatric patients.

Please click here for complete Prescribing Information, including Patient Information.

SELECT SAFETY INFORMATION FOR CALQUENCE (acalabrutinib)

INDICATION AND USAGE

CALQUENCE is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

SELECT SAFETY INFORMATION

Serious adverse events, including fatal events, have occurred with CALQUENCE, including serious and opportunistic infections, hemorrhage, cytopenias, second primary malignancies, and atrial fibrillation and flutter. The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, and diarrhea.

Please see full Prescribing Information including Patient Information.

SELECT SAFETY INFORMATION FOR TAGRISSO (osimertinib)

There are no contraindications for TAGRISSO
TAGRISSO is associated with several serious and sometimes fatal adverse reactions, including interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, erythema multiforme and Stevens-Johnson syndrome, and embryo-fetal toxicity
The most common adverse reactions (≥20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue, and decreased appetite
U.S. FDA-APPROVED INDICATIONS

TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
TAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy
Please see complete Prescribing Information, including Patient Information.

IMPORTANT SAFETY INFORMATION FOR ENHERTU (fam-trastuzumab deruxtecan-nxki)

Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
Contraindications
None.

Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer
In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Locally Advanced or Metastatic Gastric Cancer
In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0).

Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Metastatic Breast Cancer
In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients.

Locally Advanced or Metastatic Gastric Cancer
In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level.

Adverse Reactions
Metastatic Breast Cancer
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%).

Locally Advanced or Metastatic Gastric Cancer
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%).

Use in Specific Populations

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%). Of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

NOTES TO EDITORS

About AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.