On May 30, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) reported topline results from the confirmatory Phase 3 TROPiCS-04 study in locally advanced or metastatic urothelial cancer (mUC) (Press release, Gilead Sciences, MAY 30, 2024, View Source [SID1234643894]). The TROPiCS-04 study evaluated Trodelvy (sacituzumab govitecan-hziy; SG) vs. single-agent chemotherapy (treatment of physicians’ choice, TPC) in patients with mUC who have previously received platinum-containing chemotherapy and anti-PD-(L)1 therapy.

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The study did not meet the primary endpoint of overall survival (OS) in the intention-to-treat (ITT) population. A numerical improvement in OS favoring Trodelvy was observed, and trends in improvement for select pre-specified subgroups and secondary endpoints of progression-free survival (PFS) and overall response rate (ORR) were also shown. The pre-specified subgroup analyses were not alpha-controlled for formal statistical testing. These data will be presented at an upcoming medical meeting.

In the overall study population, there was a higher number of deaths due to adverse events with Trodelvy compared to TPC, which were primarily observed early in treatment and related to neutropenic complications, including infection. Gilead will further investigate these data, and is working to reiterate to treating physicians the importance of granulocyte-colony stimulating factor (G-CSF) use for the prevention of neutropenic complications. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia; please see below for Important Safety Information.

There are no changes to the known safety profile of Trodelvy for the approved breast cancer indications or other investigational uses. To date, the Trodelvy safety profile is generally well-tolerated and consistent with use in over 40,000 patients across Trodelvy’s approved indications and in clinical trials.

Gilead is continuing to analyze the data and will discuss the results and next steps with the FDA. In the U.S., Trodelvy has an accelerated approval indication for patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and anti-PD-(L)1 therapy. 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 confirmatory trials, including the TROPiCS-04 study.

Metastatic UC is an aggressive disease which most commonly affects older patients with concurrent medical morbidities and additional changes related to the aging process. Despite recent advances, survival rates remain poor with only 8% of patients living beyond five years after diagnosis. These results may in part reflect the difficulty of treating patients with mUC who have previously received platinum-containing chemotherapy and checkpoint inhibitor therapy. There is an urgent need for new treatment options to help improve long-term outcomes.

Gilead would like to thank the patients, families, investigators, and advocates who contributed to this important research. We remain committed to advancing care to address the unmet needs for the bladder cancer community.

Trodelvy is the first approved Trop-2-directed antibody-drug conjugate (ADC), which has demonstrated meaningful survival advantages in two different types of metastatic breast cancers. There are more than 20 ongoing clinical trials for Trodelvy.

Please see below for the approved U.S. Indication and additional Important Safety Information.

About Metastatic Urothelial Cancer

Bladder cancer is one of the most common cancers worldwide, with more than 1.6 million people living with the disease and urothelial cancer (UC) accounting for 90% of these cases. Metastatic bladder cancer is an aggressive disease and survival rates remain poor, with only 8% of patients living beyond five years after diagnosis. Despite recent advances, less than 20% of patients with metastatic bladder cancer go on to receive second-line therapy. There is an urgent need for new treatment options for patients with mUC who have progressed on available therapies to help improve long-term outcomes.

About the TROPiCS-04 Study

The TROPiCS-04 study is an open-label, global, multi-center, randomized Phase 3 study that evaluated Trodelvy vs. single-agent chemotherapy (treatment of physicians’ choice, TPC) in patients with locally advanced or mUC who received platinum-containing chemotherapy and checkpoint inhibitor therapy. The study enrolled 711 patients randomized 1:1 to receive either Trodelvy or one of three TPC chemotherapeutic standard of care (SOC) options: paclitaxel, docetaxel, or vinflunine. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR) and duration of objective tumor response (DoR) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and blinded independent central review (BICR). Further study details are available on clinicaltrials.gov (NCT04527991).

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast, bladder and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

Trodelvy is approved in almost 50 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

Trodelvy also has multiple global approvals for certain patients with pre-treated HR+/HER2- metastatic breast cancer, including in Australia, Brazil, Canada, the European Union, Israel, United Arab Emirates and the United States. In the U.S., Trodelvy has an accelerated approval for treatment of certain patients with second-line or later metastatic urothelial cancer; see below for full indication statements.

Trodelvy is being explored for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), head and neck cancer, gynecological cancer, and gastrointestinal cancers.

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of adult patients with:

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. 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 confirmatory trials.
U.S. Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI.

Diarrhea: Diarrhea occurred in 64% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 64% of all patients treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

Please see full Prescribing Information, including BOXED WARNING.

On May 30, 2024 Strand Therapeutics, the world’s first programmable mRNA company developing curative therapies for cancer, autoimmune diseases, and beyond, reported the first patient has been dosed in their Phase 1, first-in-human trial of STX-001, an investigational multi-mechanistic, synthetic self-replicating mRNA technology that expresses an IL-12 cytokine for an extended duration, directly into the tumor microenvironment (Press release, Strand Therapeutics, MAY 30, 2024, View Source [SID1234643893]).

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"STX-001 represents the first programmable mRNA therapy in oncology to enter the clinic for the treatment of solid tumors," said Jake Becraft, Ph.D., CEO & Co-Founder, Strand Therapeutics. "We are proud of this remarkable achievement for patients and for Strand Therapeutics to be able to take STX-001 from the lab to the clinic to evaluate the potential of this novel treatment approach for cancer patients with solid tumors."

STX-001 shows promise as a new approach to improve the efficacy of immunotherapy for solid tumors. In animal models, STX-001’s self-replicating mRNA technology induced immunogenic cancer cell death and promoted recruitment of T cells and NK cells to the tumor microenvironment, as well as their activation, by directly expressing an IL-12 payload from the synthetic mRNA directly from the tumor cells themselves.

"Significant progress has been made to date with current immunotherapies to address unmet patient needs in various solid tumors, but more work needs to be done to induce durable clinical responses in patients with minimal toxicities," said Tasuku Kitada, Ph.D., Co-Founder, President, and Head of R&D, Strand Therapeutics. "We are eager to advance our work with STX-001 and continue to pioneer the development of programmable mRNA therapies to provide targeted and precise immune activation to the tumor microenvironment."

Strand at ASCO (Free ASCO Whitepaper)

The first patient dosed with STX-001 comes days before the start of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 31 – June 4 in Chicago. Strand will present a poster on the Phase 1 trial design. The Phase 1 trial is an open-label, multi-center first-in-human dose-escalation trial, evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of STX-001 alone, or in combination with pembrolizumab in patients with treatment refractory advanced solid tumors.

Details of the presentation are as follows:

Presentation Title: A phase I trial of intratumoral STX-001: A novel self-replicating mRNA expressing IL-12 alone or with pembrolizumab in advanced solid tumors.

Session Type: Poster Session

Session Title: Developmental Therapeutics — Immunotherapy

Track: Developmental Therapeutics – Immunotherapy

Sub-Track: New Targets and Technologies (IO)

Session Date and Time: Saturday, June 1, 9:00AM – 12:00PM CDT

Location: McCormick Place, Chicago, Illinois, Hall A

Poster Board Number: 161b

Permanent Abstract Number: TPS2696

Additional meeting information is available on the ASCO (Free ASCO Whitepaper) website.

On May 30, 2024 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the company and its research collaborators will present data from 16 studies highlighting the role of Guardant blood tests and real-world data in advancing precision oncology and cancer screening at the 2024 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, May 31-June 4 in Chicago (Press release, Guardant Health, MAY 30, 2024, View Source [SID1234643892]).

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Featured presentations will share data supporting the utility of therapy response monitoring with circulating tumor DNA (ctDNA) using Guardant Infinity and the use of the GuardantINFORM clinical-genomic database to characterize drivers and resistance mechanisms and their association with real-world outcomes in a variety of solid tumor types. Additional studies will present data supporting the application of genomic and epigenomic biomarkers in areas such as minimal residual disease detection and cohort characterization.

"The robust data we present at ASCO (Free ASCO Whitepaper) will further demonstrate the important scientific and clinical developments in cancer care that are possible using liquid biopsy," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "Several studies will highlight the tremendous potential of epigenomic analysis using our Guardant Infinity platform to quantify tumor fraction and characterize therapy resistance mechanisms in order to improve treatment response across multiple cancer types."

Featured presentations include:

An oral presentation of a study using the Guardant360 liquid biopsy and exploring racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer (Abstract 1017, Monday, June 3, 11:30 am – 1:00 pm, Hall D1)
Interim data readout from the collaboration between Guardant Health and the Parker Institute for Cancer Immunotherapy (PICI) to identify genomic and epigenomic biomarkers using Guardant Infinity for quantification of tumor fraction and association with outcomes from the RADIOHEAD real-world advanced pan-cancer cohort (Abstract 2570, Saturday, June 1, 9:00 am – 12:00 pm, Hall A)
Complete list of Guardant Health and collaborator presentations at ASCO (Free ASCO Whitepaper)

Abstract

Title (Hall A unless otherwise noted)

Product

Saturday, June 1 | 9:00 am – 12:00 pm

2570

Use of a tissue-free epigenomic circulating tumor DNA (ctDNA) assay for quantification of tumor fraction (TF) and association with outcomes from RADIOHEAD real-world advanced pan-cancer cohort

Guardant Infinity

3041

Association of KRAS G12D vs. G12V circulating tumor DNA variant allele fraction and real-world overall survival in metastatic non-small cell lung and colorectal cancers

Guardant Infinity

Saturday, June 1 | 1:30 pm – 4:30 pm

LBA3557

A randomized study evaluating tailoring of advanced/metastatic colorectal cancer (mCRC) therapy using circulating tumor DNA (ctDNA): TACT-D

Guardant360 CDx

3519

Candidate molecular alterations associated with potential resistance in KRAS G12D gastrointestinal cancers

Guardant360 & Guardant360/CDx

3602

Characteristics of patients (pts) with disease relapse despite absence of molecular residual disease (MRD) after resection of colorectal oligometastases (CRM): implications from PRECISION study

Guardant360 & Guardant Reveal

3545

Characterization of mutational signatures demonstrating adaptive mutability post anti-EGFR therapy in a real-world metastatic colorectal cancer cohort

GuardantINFORM

Sunday, June 2 | 9:00 am – 12:00 pm

1037

Molecular profiling of serial liquid biopsy specimens utilizing cell free DNA (cfDNA) and circulating tumor cells (CTCs) in TBCRC041: A phase II study of alisertib in endocrine resistant metastatic breast cancer (MBC)

Guardant Infinity

1043

Evaluating metrics of circulating tumor DNA response and progression using a high sensitivity tumor-agnostic assay in metastatic HR+/HER2- breast cancer receiving endocrine therapy and a CDK4/6-inhibitor

Guardant Infinity

1071

Real-world (RW) elacestrant use patterns and therapeutic outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC)

GuardantINFORM

5069

Dynamic androgen receptor alterations (ARa) ctDNA profiles and clinical outcomes in metastatic prostate cancer (mPC)

GuardantINFORM

Monday, June 3 | 9:00 am – 12:00 pm | Hall A

5592

Serial circulating tumor DNA (ctDNA) sequencing to monitor response and define acquired resistance to letrozole/abemaciclib in endometrial cancer (EC)

Guardant Infinity

Monday, June 3 | 11:30 am – 1:00 pm | Hall D1

1017

Rapid Oral Abstract Session: Racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer

Guardant360

Online only

e13097

Co-occurrence of ESR1 and PIK3CA mutations in HR+/HER2- metastatic breast cancer: Incidence and outcomes with targeted therapy

Guardant360 & Guardant360 CDx

e12566

Molecular profiling in ABC: Is complementary testing with tissue and plasma necessary and clinically relevant?

Guardant360

e13702

Utilization of circulating tumor DNA (ctDNA) testing by race and ethnicity in more than 135,000 patients

GuardantINFORM

e20088

Use of cell-free tumor DNA in early detection of lung cancer

Shield (next generation)

The full abstracts for Guardant Health and a list of all abstracts being presented at the meeting can be found at the ASCO (Free ASCO Whitepaper) website.

For more information and updates from the meeting, follow Guardant Health on LinkedIn and X (Twitter) or visit ASCO (Free ASCO Whitepaper) booth #28115.

On May 30, 2024 Sarah Cannon Research Institute (SCRI), one of the world’s leading oncology research organizations conducting community-based clinical trials, reported that it will highlight its latest research insights through more than 145 presentations at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from Friday, May 31 – Tuesday, June 4 in Chicago, Ill (Press release, Sarah Cannon Research Institute, MAY 30, 2024, View Source [SID1234643891]). Over 100 investigators from across SCRI’s network are co-authors on clinical trial updates that will be showcased at the Annual Meeting, including data from more than 65 early-phase clinical trials.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"We look forward to connecting with colleagues from around the world at ASCO (Free ASCO Whitepaper)’s Annual Meeting to discuss the latest developments in advancing therapies for cancer patients," says Howard A. "Skip" Burris, III, MD, President, SCRI. "The depth and breadth of clinical research being presented by SCRI experts signifies our commitment to accelerating drug development and providing greater access to cutting-edge therapies closer to home."

For a comprehensive list of abstracts and presentations, visit SCRI’s ASCO (Free ASCO Whitepaper) Site. To learn more about our research experts, visit our Leadership Page.

Noteworthy Presentations

Breast Cancer

Erika Hamilton, MD, SCRI, will present "H3B-6545 in Women with Locally Advanced/Metastatic Estrogen Receptor-Positive, HER2 Negative Breast Cancer" in an oral presentation during the Breast Cancer – Metastatic Rapid Oral Abstract Session on Monday, June 3 from 11:30 a.m. – 1:00 p.m. CDT in Hall D1.
Joyce O’Shaughnessy, MD, SCRI at Texas Oncology I The US Oncology Network, will deliver "Association of MammaPrint Index and 3-Year Outcome of Patients with HR+HER2- Early-Stage Breast Cancer Treated with Chemotherapy with or without Anthracycline" in an oral presentation during the Breast Cancer—Local/Regional/Adjuvant Rapid Oral Abstract Session on Friday, May 31 from 2:45 p.m. – 4:15 p.m. CDT in E451.
Denise Yardley, MD, SCRI, will give the oral presentation, "Baseline Characteristics and Efficacy Endpoints for Patients with Node-Negative HR+/HER2− Early Breast Cancer: NATALEE Trial" during the Breast Cancer—Local/Regional/Adjuvant Rapid Oral Abstract Session on Friday, May 31 from 2:45 p.m. – 4:15 p.m. CDT in E451.
Lung Cancer

David Spigel, MD, SCRI, will discuss "ADRIATIC: Durvalumab as Consolidation Treatment for Patients with Limited-Stage Small-Cell Lung Cancer" in an oral presentation during the Plenary Session on Sunday, June 2 from 1:00 p.m. – 4:00 p.m. CDT in Hall B1.
Clinical Trial Access

Ishwaria Subbiah, MD, MS, SCRI, will present "5-Year Multicenter Analysis of Clinical Trial Participation and Total Cost of Care for Older Adults with Cancer" in an oral presentation during the Quality Care/Health Services Research Rapid Oral Abstract Session on Monday, June 3 from 1:15 p.m. – 2:45 p.m. CDT in S102.
In addition to scientific presentations, SCRI leadership will participate in and lead ASCO (Free ASCO Whitepaper) sessions, including:

Meredith McKean, MD, MPH, SCRI, is a discussant in the Oral Abstract Session, Melanoma/Skin Cancers, on Friday, May 31 from 2:45 p.m. – 5:45 p.m. CDT in Hall D1, where she will present "PD-1–Refractory Advanced Melanoma: How Do We Get to the Finish Line?"
Dr. Burris will deliver the "Presentation and Recognition of Conquer Cancer Top Donors" in the Opening Session on Saturday, June 1 from 9:30 a.m. – 12:00 p.m. CDT in Hall B1.
Dr. Hamilton will chair the Clinical Science Symposium, Next-Generation Antibody-Drug Conjugates: The Revolution Continues, and present "The ABCs of ADCs: What Does the Future Hold?" on Sunday, June 2 from 9:45 a.m. – 11:15 a.m. CDT in Hall D1.
Abdul Naqash, MD, SCRI at OU Health – Stephenson Cancer Center, will chair the Oral Abstract Session, Developmental Therapeutics—Immunotherapy, on Monday, June 3 from 11:30 a.m. – 2:30 p.m. CDT in Hall D2.
Andrew McKenzie, PhD, SCRI & Genospace, and Vivek Subbiah, MD, SCRI, will serve as panelists in the Case-Based Panel, Beyond Tumor Types: Advancing Tumor-Agnostic Drug Development and the Role of the Tumor Microenvironment, on Monday, June 3 from 3:00 p.m. – 4:00 p.m. CDT in Hall D2.
Cesar Perez, MD, SCRI at Florida Cancer Specialists & Research Institute, will present "Emerging Data for Antibody Drug Conjugates in Head and Neck Squamous Cell Carcinoma," during the Breaking Ground in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Novel Therapies Beyond PD-L1 Immunotherapy Education Session on Tuesday, June 4 from 8:00 a.m. – 9:15 a.m. CDT in S100a.
Additional Poster Presentations with SCRI First Authors

Saturday, June 1

"Validation of PD-L1 as a Predictive Biomarker of Response in Operable Gastroesophageal Adenocarcinoma: A Meta-Analysis and Meta-Regression of Neoadjuvant Chemoimmunotherapy Trials," Antonella Cammarota, MD, SCRI at HCA Healthcare UK, 1:30 p.m. – 4:30 p.m. CDT, Hall A.
"Phase 1 Trial Safety and Efficacy of Ragistomig, a Bispecific Antibody Targeting PD-L1 and 4-1BB, in Advanced Solid Tumors," Gerald Falchook, MD, SCRI at HealthONE, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
"NALIRIFOX versus Nab-Paclitaxel and Gemcitabine in Treatment-Naïve Patients with Metastatic Pancreatic Ductal Adenocarcinoma: Updated Overall Survival Analysis with 29-Month Follow-Up of NAPOLI 3," Maen Hussein, MD, SCRI at Florida Cancer Specialists & Research Institute, 1:30 p.m. – 4:30 p.m. CDT, Hall A.
"Safety and Preliminary Efficacy of EIK1001 in Combination with Atezolizumab in Participants with Advanced Solid Tumors," & "Preliminary Results from a Phase 1 Study of AC699, an Orally Bioavailable Chimeric Estrogen Receptor Degrader, in Patients with Advanced or Metastatic Breast Cancer," Manish Patel, MD, SCRI at Florida Cancer Specialists & Research Institute, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
"Results from Phase 1a/1b Analyses of TTX-080, a First in Class HLA-G Antagonist, in Combination with Cetuximab in Patients with Metastatic Colorectal Cancer and Head and Neck Squamous Cell Carcinoma," Susanna Ulahannan, MD, MMEd, SCRI at OU Health – Stephenson Cancer Center, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
"Phase 1/2 Study of NGM707, an ILT2/ILT4 Dual Antagonist Antibody, in Advanced Solid Tumors: Interim Results from Dose-Escalation," Judy Wang, MD, SCRI at Florida Cancer Specialists & Research Institute, 9:00 a.m. – 12:00 p.m. CDT, Hall A
Sunday, June 2

"Trastuzumab Deruxtecan vs Trastuzumab Emtansine in Patients with HER2+ Metastatic Breast Cancer: Updated Survival Results of DESTINY-Breast03," Dr. Hamilton, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
Monday, June 3

"Subcutaneous Epcoritamab Administered Outpatient for Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Follicular Lymphoma: Results from Phase 2 EPCORE NHL-6," David Andorsky, MD, SCRI at Rocky Mountain Cancer Centers I The US Oncology Network, 9 a.m. – 12 p.m. CDT, Hall A
"MYTX-011 in Patients with Previously Treated Locally Advanced or Metastatic NSCLC: Initial Dose Escalation Results in The Phase 1 KisMET-01 Study," Melissa Johnson, MD, SCRI, 1:30 p.m. – 4:30 p.m. CDT, Hall A.
"Clinical Activity and Safety of Naptumomab Estafenatox and Docetaxel in Patients with Checkpoint Inhibitor –Pretreated Advanced/Metastatic Non-Small Cell Lung Cancer: Preliminary Results of a P2 Trial," Tim Larson, MD, SCRI at Minnesota Oncology I The US Oncology Network, 1:30 p.m. – 4:30 p.m. CDT, Hall A.
"Treatment of Acute Myeloid Leukemia with Orca-T," Jeremy Pantin, MD, SCRI at TriStar Centennial, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
"Safety and Tolerability of Durvalumab + Carboplatin/Paclitaxel Followed by Durvalumab ± Olaparib in Patients with Newly Diagnosed Advanced or Recurrent Endometrial Cancer in the DUO-E/GOG-3041/ENGOT-EN10 Trial," Jessica Thomes Pepin, MD, SCRI at Minnesota Oncology I The US Oncology Network, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
"OPTec: A Phase 2 Study to Evaluate Outpatient Step-Up Administration of Teclistamab, a BCMA-Targeting Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma," Robert Rifkin, MD, SCRI at Rocky Mountain Cancer Centers I The US Oncology Network, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
"Clinical Trial Participation and End-of-Life Care Among Older Adults: A Multi-Center Longitudinal Observational Cohort Analysis of 121,717 Patients with Cancer," Dr. I. Subbiah, 9:00 a.m. – 12:00 p.m. CDT, Hall A.
"Performance of Comprehensive Genomic Profiling versus Single Gene Testing in Guideline-Recommended Biomarker Selection in Non-Small Cell Lung Cancer," Dr. V. Subbiah, 1:30 p.m. – 4:30 p.m. CDT, Hall A.

On May 30, 2024 Akeso, Inc. (HKEX: 9926.HK) ("Akeso," "we," or the "Company") reported that the Phase III clinical trial, HARMONi-2 or AK112-303, met its primary endpoint of progression-free survival (PFS) (Press release, Akeso Biopharma, MAY 30, 2024, View Source [SID1234643890]). HARMONi-2 evaluated monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 TPS >1%). HARMONi-2 is a single region, multi-center, double-blinded Phase III study sponsored by Akeso with data generated and analyzed by Akeso.

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At a prespecified interim analysis conducted by an independent Data Monitoring Committee, ivonescimab demonstrated a statistically significant and clinically meaningful improvement in PFS by blinded independent radiology review committee (BICR) compared to pembrolizumab. The PFS benefit was demonstrated across clinical subgroups, including those with PD-L1 low expression (PD-L1 TPS 1-49%), PD-L1 high expression (PD-L1 TPS >50%), squamous and non-squamous histologies, as well as other high-risk patients.

There are no known Phase III clinical trials in NSCLC which have shown a statistically significant improvement compared to pembrolizumab in a head-to-head setting.

The Phase III HARMONi-2 study, along with the approval of ivonescimab in China in combination with chemotherapy based on the results of the HARMONi-A trial, provides clear evidence supporting the purposefully-engineered, differentiated mechanism of action of ivonescimab, a PD-1 / VEGF bispecific antibody evidencing cooperative binding characteristics, and its opportunity to improve upon the existing standards of care for solid tumors.

"HARMONi-2 clearly demonstrates that ivonescimab has strong clinical values globally as well as commercial potentials." stated Dr. Michelle Xia , Chairwoman, President and Chief Executive Officer of Akeso. "ivonescimab is the next generation in PD-1 directed immunotherapy, and its potential to make a significant difference in the lives of patients with lung cancer and prospectively other tumors."

Conference Call

Akeso, Inc. (HKEX: 9926.HK) ("Akeso," "we," or the "Company") will host a conference call to discuss recent updates related to ivonescimab on Friday May 31, 2024, before the market opens.

About Ivonescimab

Ivonescimab, known as AK112 is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro.[1] This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days,[1] is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials, HARMONi and HARMONi-3.

The safety profile of ivonescimab is manageable and consistent with known risks for PD-1 and VEGF inhibiting drugs. In the first Phase III study to be presented at ASCO (Free ASCO Whitepaper), "Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous NSCLC who progressed on EGFR TKI treatment (AK112-301): A randomized, double-blind, multi-center, phase 3 trial," 5.6% of patient discontinues ivonescimab due to adverse events.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to a placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR TKI (e.g., osimertinib).

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.

About Lung Cancer

Lung cancer is believed to impact approximately 600,000 people across the United States, United Kingdom, Spain, France, Italy, Germany, and Japan.[2] NSCLC is the most prevalent type of lung cancer and represents approximately 80% to 85% of all incidences.[3] Among patients with non-squamous NSCLC, approximately 15% have EGFR-sensitizing mutations in the United States and Europe.[4] Patients with squamous histology represent approximately 25% to 30% of NSCLC patients.