On December 6, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) reported new data from a post-hoc analysis from the Phase 3 TROPiCS-02 study evaluating Trodelvy (sacituzumab govitecan-hziy; SG) versus comparator chemotherapy (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- metastatic breast cancer who progressed on endocrine-based therapies and at least two chemotherapies (Press release, Gilead Sciences, DEC 6, 2022, View Source;Metastatic-Breast-Cancer [SID1234624865]). In the analysis, Trodelvy improved progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) compared with TPC across Trop-2 expression levels. Details of the late-breaking abstract will be presented today at the 2022 San Antonio Breast Cancer Symposium (SABCS, Abstract #GS1-11).

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"Sacituzumab govitecan improved both progression-free survival and overall survival in pre-treated HR+/HER2- metastatic breast cancer in the Phase 3 TROPiCS-02 study compared to standard chemotherapy options. This post-hoc analysis demonstrates that the level of Trop-2 expression on an individual’s tumor did not impact sacituzumab govitecan efficacy," said Dr. Hope Rugo, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center, U.S. "These data can give us confidence in the potential benefit of sacituzumab govitecan for patients with endocrine-resistant metastatic breast cancer who have progressed on available chemotherapies, across Trop-2 expression levels."

Trop-2, a protein found on the surface of cancer cells, is involved in several cellular processes regulating cancer growth and invasion. It is highly expressed in most human solid tumors, including more than 90% of breast cancers. In the TROPiCS-02 study, Trop-2 expression was measured by immunohistochemistry and expressed as a histochemical score (H-score; range, 0-300). Efficacy outcomes were assessed across H-score groups, including those with very low Trop-2 expression. Across each H-score subgroup, Trodelvy demonstrated improved PFS, OS and ORR compared to TPC, which is consistent with the PFS, OS and ORR in the TROPiCS-02 intention-to-treat population.

"The prognosis for patients with pre-treated HR+/HER2- metastatic breast cancer who have developed resistance to endocrine-based therapies has been poor, and these TROPiCS-02 study results demonstrate clinical efficacy with Trodelvy, across Trop-2 expression levels," said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. "Our ambition is to continue our impact beyond our current approval in second-line metastatic TNBC, and we look forward to advancing discussions with the U.S. FDA and global health authorities to help bring Trodelvy to more people living with metastatic breast cancer."

The safety profile for Trodelvy in TROPiCS-02 was consistent with prior studies, with no new safety signals identified in this population.

Detailed statistically significant and clinically meaningful PFS and OS results from the Phase 3 TROPiCS-02 study were presented at ASCO (Free ASCO Whitepaper) 2022 and ESMO (Free ESMO Whitepaper) 2022, respectively. Based on these data, the U.S. Food and Drug Administration (FDA) accepted for priority review the supplemental Biologics License Application (sBLA) for Trodelvy in adult patients with unresectable locally advanced or metastatic HR+/HER2- (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. The Prescription Drug User Fee Act (PDUFA) target action date is currently set for February 2023.

Trodelvy has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

Summary of post-hoc analysis results by Trop-2 expression

Trop-2
expression,
H-score

n (SG/TPC)

Median PFS
(SG vs
TPC),
months

PFS Hazard
Ratio
(95%CI)

Median OS
(SG vs
TPC),
months

OS Hazard
Ratio
(95%CI)

<100

96/96

5.3 vs. 4.0

0.77
(0.54-1.09)

14.6 vs. 11.3

0.75
(0.54-1.04)

≥100

142/128

6.4 vs. 4.1

0.60
(0.44-0.81)

14.4 vs. 11.2

0.83
(0.62-1.11)

≤10

34/45

5.5 vs. 4.3

0.89
(0.51-1.57)

17.6 vs. 12.3

0.61
(0.34-1.08)

>10-<100

62/51

5.0 vs. 3.5

0.67
(0.42-1.07)

13.7 vs. 11.0

0.81
(0.54-1.23)

>10

204/179

5.6 vs. 4.0

0.62
(0.48-0.80)

14.1 vs. 11.1

0.82
(0.65-1.0)

H-score, histochemical score; OS, overall survival; PFS, progression-free survival; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.

Additional Abstracts across Gilead’s Breast Cancer Franchise at 2022 SABCS:

Gilead is also presenting a number of other abstracts at the congress, including patient-reported outcomes data from TROPiCS-02, and in preclinical research and trials in progress in metastatic triple-negative breast cancer (TNBC). Accepted abstracts at SABCS 2022 include (all times CDT):

Abstract Disposition

Abstract Title

Oral Presentation

Presentation # GS1-11
Tuesday, Dec. 6
4:30 PM

Sacituzumab Govitecan (SG) vs. Treatment of Physician’s Choice (TPC) by Trop-2 Expression in the TROPiCS-02 Study of Patients (Pts) With HR+/HER2- Metastatic Breast Cancer (mBC)

Poster Presentations

Poster # P3-07-08
Wednesday, Dec. 7
5:00 PM

Exposure-Adjusted Incidence Rates (EAIRs) of Adverse Events (AEs) From the Phase 3 TROPiCS-02 Study of Sacituzumab Govitecan (SG) vs Treatment of Physician’s Choice (TPC) in HR+/HER2- Metastatic Breast Cancer

Poster # P4-07-65

Thursday, Dec. 8

7:00 AM

Effect of Sacituzumab Govitecan vs Chemotherapy in HR+/HER2- Metastatic Breast Cancer: Patient-Reported Outcomes From the TROPiCS-02 Trial

Poster # P4-07-12
Thursday, Dec. 8
7:00 AM

Development of Triple-Negative Breast Cancer (TNBC) Syngeneic Models and TROP2-Directed Antibody-Drug Conjugate (ADC) Surrogate to Model Therapeutic Combinations

Poster # OT2-10-01
Wednesday, Dec. 7
5:00 PM

A Phase 2, Randomized Study of Magrolimab Combination Therapy in Adult Patients With Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer (TiP)​

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 and bladder 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 microenvironment.

Trodelvy is approved in more than 40 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 is also approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

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

U.S. Indications for Trodelvy

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

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC 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 a confirmatory trial.
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. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late 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 61% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. 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.

Diarrhea: Diarrhea occurred in 65% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of 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 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with Trodelvy and Grade 3 nausea occurred in 4% of these patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% 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 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 11% 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 ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, 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 TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, any infection, alopecia, anemia, decreased appetite, constipation, vomiting, abdominal pain, and rash. 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 substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

Please see full Prescribing Information, including BOXED WARNING.

On December 6, 2022 Hologic, Inc. (Nasdaq: HOLX) and its subsidiary, Biotheranostics, Inc., reported new study data showing that the Breast Cancer Index test identified which premenopausal patients with early-stage, hormone-receptor positive (HR+) breast cancer benefited from the addition of ovarian function suppression (OFS) to primary adjuvant endocrine therapy (Press release, Hologic, DEC 6, 2022, View Source [SID1234624864]). The Breast Cancer Index test is the first biomarker to be evaluated in a cohort from the landmark Suppression of Ovarian Function Trial (SOFT). The translational study results are featured in the official press program at the 2022 San Antonio Breast Cancer Symposium (SABCS) being held from December 6-10, 2022.1 Full study results were presented during the general session #GS1-06 on December 6 at 3:15 p.m. CST.

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"There is a significant need for biomarkers to aid in treatment decisions for premenopausal women with breast cancer. Our study presented at SABCS is the first to examine a biomarker’s ability to determine benefit of ovarian function suppression in these women," said Dr. Ruth O’Regan, Chair of Medicine and Charles A. Dewey Professor at the University of Rochester. "These data found that the Breast Cancer Index test identified women who received benefit from ovarian function suppression as well as those who did not, which is incredibly important given the potential impact of this more intensive treatment approach in young women. While these data are promising, we look forward to further investigating the test’s utility to help inform ovarian function suppression treatment decisions in the future."

The landmark SOFT trial was an international, three-arm, non-blinded, randomized clinical trial of 3,066 premenopausal women with HR+ breast cancer. The trial demonstrated that the addition of OFS to five years of primary adjuvant endocrine therapy (either tamoxifen or exemestane) reduced the risk of recurrence compared to adjuvant tamoxifen alone.2 OFS typically involves hormonal drug injections with a gonadotropin-releasing hormone (GnRH) agonist or surgical removal of the ovaries (bilateral oophorectomy).3 In an effort to evaluate the potential of a biomarker to assist in patient selection for this more intensive approach, the new study presented at SABCS evaluated the predictive and prognostic ability of the Breast Cancer Index test in a cohort of patient tumor samples (n=1,717) from the SOFT trial. Notably, the patient characteristics in this retrospective translational study were highly representative of the original SOFT trial.

The data found that the Breast Cancer Index genomic assay identified which premenopausal women with early-stage, HR+ breast cancer benefited from more intensive endocrine therapy (exemestane plus OFS) compared to tamoxifen alone. The Breast Cancer Index test identified 58% of women who benefited from the addition of OFS, experiencing an absolute benefit of 11.6%, compared with 42% who did not benefit (p<0.01 in adjusted analysis). The data also found that the Breast Cancer Index test’s predictive performance was generally consistent across subgroups, including nodal status, prior chemotherapy, age and HER2-negative patients. Compared to the benefit shown with exemestane plus OFS versus tamoxifen alone, the benefit for tamoxifen plus OFS versus tamoxifen alone was smaller, which is consistent with data reported from the SOFT trial itself. The study also confirmed the prognostic value of the Breast Cancer Index test, as women with higher Breast Cancer Index test risk scores were more likely to experience disease recurrence.

"Multiple clinical studies and national oncology guidelines affirm the predictive ability of the Breast Cancer Index test for extended endocrine therapy," said Kevin Thornal, Group President, Global Diagnostic Solutions at Hologic. "These new data further establish the Breast Cancer Index test as a significant endocrine response biomarker and reveal additional predictive capabilities of the test. As we explore its predictive power earlier in a patient’s journey, we aim to uncover broader potential clinical utility in more women with early-stage, HR+ breast cancer."

About the Breast Cancer Index Test

The Breast Cancer Index test is a molecular, gene expression-based test uniquely positioned to provide information to help physicians individualize treatment decisions for patients with early-stage, HR+ breast cancer. This breakthrough test helps oncologists and patients navigate the difficult trade-offs between taking steps to prevent recurrence of their disease and facing significant side effects and safety challenges related to unnecessary treatment. The Breast Cancer Index test has guideline designation from the American Joint Committee on Cancer for cancer staging based on molecular profile. The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the European Group on Tumor Markers (EGTM) and St. Gallen acknowledge the Breast Cancer Index test as a biomarker to inform the chemotherapy decision; and ASCO (Free ASCO Whitepaper), EGTM and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) acknowledge the Breast Cancer Index test as a biomarker to inform the extended endocrine treatment decision.4 It is the only validated, commercially available test that predicts benefit from extended endocrine therapy. The Breast Cancer Index test is intended for routine clinical use, and treatment decisions based on results are the responsibility of the physician. It is a laboratory developed test (LDT) performed in a single CLIA-certified and CAP-accredited diagnostic laboratory and is not required to be cleared or approved by the U.S. Food and Drug Administration. For more information, visit www.breastcancerindex.com.

On December 6, 2022 Researchers at Exai Bio and UCSF reported data demonstrating that Exai’s novel, RNA-based liquid biopsy platform accurately detected breast cancer at the earliest stages and for the smallest tumors (Press release, Exai Bio, DEC 6, 2022, View Source [SID1234624863]). Earlier detection of breast cancer is crucial for optimal patient outcomes but cannot always be achieved based on symptoms or mammography.

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Exai’s technology uses RNA sequencing to identify a novel category of cancer-associated, small non-coding RNAs, termed orphan non-coding RNAs (oncRNAs). In a poster entitled, "Early-stage breast cancer detection using orphan noncoding RNAs", presented at the 2022 San Antonio Breast Cancer Symposium, Exai demonstrated that oncRNA biomarkers in blood, combined with machine learning, detected breast cancer with high accuracy overall, including across all cancer stages and tumor sizes. The poster also showed that even at the earliest stages and smallest tumors, sensitivity was greater than 80% at 95% specificity. These findings suggest that Exai’s liquid biopsy test for earlier detection of cancer will improve care and outcomes for cancer patients.

OncRNAs are secreted from cancer cells and are abundant in the blood of cancer patients. Exai has created a catalog of hundreds of thousands of oncRNAs from all major cancer types. This vast catalog gives the Exai platform several scientific and practical advantages over tests that focus on circulating tumor DNA.

These SABCS 2022 results complement and build on breast cancer data presented at SABCS 2021, where changes in oncRNAs reflected breast cancer treatment response, predicted overall survival and added significant information to standard clinical endpoints such as tumor tissue pathology.

With this study, Exai demonstrated again that oncRNAs can be used as a biomarker for earlier cancer detection from a blood sample. Exai recently presented results from a colorectal cancer patient cohort at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting, where Exai’s RNA-based platform accurately detected colorectal cancer at the earliest stages and for the smallest tumors.

"Our results presented at SABCS 2022 represent another important step in establishing the role of oncRNAs in addressing the unmet need of detecting cancer at its earliest stages from a simple blood sample," said Patrick Arensdorf, Chief Executive Officer of Exai. "The oncRNA-based liquid biopsy technology will be compatible with standard blood sample requirements enabling easy integration into conventional clinical workflows. Exai’s goal is to improve patient care with a variety of liquid biopsy tests for early cancer detection and monitoring of residual disease and recurrence in multiple types of cancer."

This poster will be available on-demand on the website for SABCS attendees (www.sabcs.org) beginning December 6, 2022. The poster will also be accessible on Exai’s website.

Details of the SABCS 2022 poster presentation:
Title: Early-stage breast cancer detection using orphan noncoding RNAs
Poster ID: P1-05-18
Abstract category: Detection/Diagnosis
Authors: Taylor Cavazos, Jeffrey Wang, Oluwadamilare I. Afolabi, Alice Huang, Dung Ngoc Lam, Seda Kilinc, Jieyang Wang, Lisa Fish, Xuan Zhao, Andy Pohl, Helen Li, Kimberly Chau, Patrick Arensdorf, Fereydoun Hormozdiari, Hani Goodarzi, Babak Alipanahi

On December 6, 2022 Akeso Inc. (HKEX Code: 9926.HK, "Akeso", or the "Company"), a commercial-stage biopharmaceutical company focused on developing and commercializing first-in-class and best-in-class innovative medicines globally, reported a collaboration and license agreement (the "Agreement") with Summit Therapeutics Inc. (NASDAQ: SMMT) (the "Summit"), to out-license its breakthrough bispecific antibody, ivonescimab (PD-1/VEGF, AK112) for development and commercialization in the United States, Canada, Europe, and Japan (the "License Territories") (Press release, , DEC 6, 2022, View Source [SID1234624861]). In addition, the Company will co-brand the product in the License Territories.

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Ivonescimab, known as AK112 in China and Australia and also as SMT112 in the License Territories, is a novel, potential first-in-class bispecific antibody independently developed by the Company. Ivonescimab combines the power of immunotherapy via a blockade of PD-1 with the anti-angiogenesis benefits of an anti-VEGF into a single molecule. It is our belief that the novel design has the potential to reduce side effects and safety concerns. Ivonescimab is believed to be the PD-1 / VEGF bispecific antibody that is most advanced in the clinic: there are no known PD-1-based bispecific antibodies approved by the US Food and Drug Administration ("FDA") or the European Medicines Agency ("EMA").

Currently, Akeso is conducting a phase III clinical trial of ivonescimab monotherapy versus pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III clinical trial of Ivonescimab plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy is ongoing. Ivonescimab has received breakthrough therapy designation status in China from the NMPA for three indications: the two aforementioned indications, as well as combined with docetaxel for the treatment of locally advanced or metastatic NSCLC patients who failed to prior PD-(L)1 inhibitor combined with platinum-based doublet chemotherapy.

As presented at ASCO (Free ASCO Whitepaper) 2022, ivonescimab treatment was associated with an overall response rate (ORR) in a Phase II study in patients with NSCLC who have failed EGFR-TKI’s of 68.4% and a median Progression-Free Survival (mPFS) time period of 8.2 months when combined with combination chemotherapy (pemetrexed and carboplatin) as compared to historical mPFS of 4.3 months in patients treated with combination chemotherapy (pemetrexed and platinum-based chemotherapy) alone, the current standard of care. In a separate cohort, ivonescimab combined with docetaxel in patients who have failed PD-(L)1 and chemo therapies demonstrated a mPFS of 6.6 months as compared to a historical mPFS of 4.5 months with docetaxel alone, a current standard of care regimen for these patients. The study which similarly had patients receiving ivonescimab plus chemotherapy as their first line therapy for metastatic disease, was considered to have demonstrated a tolerable safety profile and a low discontinuation rate for adverse events.

"Ivonescimab has demonstrated the potential to deliver superior clinical benefit for patients." said Dr. Michelle Xia, co-founder, Chairwoman, CEO, and President of Akeso, "The Akeso team has been dedicated to the development of ivonescimab in the past 8 years and advanced the molecule to the clinical Phase III stage. The global value of ivonescimab awaits great work from a great team to realize. We are so pleased to partner with the world-class Summit team, who has the track record of successfully bringing over a dozen indications to market for the first-in-class blockbuster drug IMBRUVICA (ibrutinib). Following intense and in-depth strategic, scientific, and operational discussion on ivonescimab between the Akeso and Summit teams in recent months, we are more confident than ever on a winning path for ivonescimab’s global development. With this tremendous momentum, we look forward to the swift execution of clinical development and commercial plan in a global setting for ivonescimab."

"The partnership between Summit and Akeso is a strategically compelling opportunity," stated Robert W. Duggan, Chairman and Chief Executive Officer of Summit. "It represents bringing together Akeso’s extraordinary team, which has built an innovation engine capable of creating novel bispecific technologies, and the talented members of team Summit with their proven track record of success of global clinical development, regulatory approvals, and commercialization, particularly in oncology. We believe the potential exists for enormous creation through this partnership. We are extremely encouraged by ivonescimab and the potential for improving the quality and duration of patients’ lives based on clinical data to support this point. Summit team is honored and enthusiastic to partner with Akeso. Our shared mission and vision are to create a significant difference for the betterment of patient healthcare outcomes around the world."

"After reviewing a substantial number of opportunities, much of which was focused on potential treatments for solid tumors, we have found the ideal partnership with the potential to change the paradigm for treating patients facing difficult odds with devastating diagnoses," added Dr. Maky Zanganeh, Co-Chief Executive Officer, President, and a member of Summit’s Board of Directors. "Ten years ago, metastatic lung cancer patients rarely survived for more than ten to twelve months from diagnosis. Today, survival can be measured in years. Our goal is to improve the quality of life of a patient facing immeasurable odds while extending the duration of that patient’s life. Our focus is always on how we can improve the lives of patients. We sought patient-friendly medicinal therapies through our search to expand our pipeline portfolio, and we are proud to take this meaningful step towards accomplishing this goal. We have significant work to do, but we are steadfastly committed to bringing ivonescimab into the hands of patients who need it most. We are thrilled to reach this agreement with Michelle and the team at Akeso, and we are excited to make this vision a reality. I am proud of Summit team who have diligently worked these past few months to establish a strong bond with the team at Akeso, and I would like to thank the talented people of Team Akeso for spending so much quality time creating this meaningful partnership."

Under the terms of the Agreement, Akeso will receive US$500 million upfront payment and the total potential deal value is up to US$5 billion including regulatory and commercial milestone payments. And Akeso will also receive low double-digit percentage of royalties on net product sales of ivonescimab. The Summit will receive the exclusive rights to develop and commercialize ivonescimab (SMT112) in the United States, Canada, Europe, and Japan. Akeso will retain development and commercialization rights for the rest of the world including China. In addition, Dr. Michelle Xia will be appointed as one member of the board of directors of Summit. The deal is subject to customary closing practices, including applicable waiting periods under the Hart-Scott-Rodino (HSR) Act.

On December 6, 2022 REVEAL GENOMICS, S.L., a Barcelona-based biotechnology start-up seeking to revolutionize precision oncology through biomarker innovation, reported positive results for HER2X in a range of clinical scenarios, demonstrating the test’s reliability (Press release, REVEAL GENOMICS, DEC 6, 2022, View Source [SID1234624860]). This new validation data confirms its suitability for general use in clinical practice.

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The results of 4 studies (APT, ATEMPT, DAPHNe and GOM) have been made public during the San Antonio Breast Cancer Symposium (SABCS), held from December 6 to 10 in San Antonio, Texas (USA).

"We are delighted to share important new results for HER2DX during SABCS, which confirm the robust ability of the test to predict long-term survival and response to anti-HER2 therapy. The HER2DX risk score and pCR score have now been validated across more than 1800 and 800 patients, respectively," says Dr. Aleix Prat, Co-founder and CSO of REVEAL GENOMICS.

"These extraordinary results will undoubtedly be key to achieving our goal of making HER2DX available globally and reaching all patients with HER2+ breast cancer. We are very excited about what the future holds for us as a company," adds Dr. Patricia Villagrasa-Gonzalez, Co-founder and CEO of REVEAL GENOMICS.

APT and ATEMPT studies: confirming the HER2DX️ risk score

The analysis of the HER2DX in the APT and ATEMPT studies is the result of the agreement between REVEAL GENOMICS and Dana-Farber Cancer Institute (US), consisting of using the test to analyze tumor samples from 471 patients with early-stage HER2+ breast cancer from both Phase II trials.

The APT clinical trial, published in the New England Journal of Medicine in 2015, demonstrated that a de-escalation treatment strategy based on weekly paclitaxel during three months and one year of trastuzumab is highly efficacious for a large proportion of stage 1 patients.

The ATEMPT clinical trial, published in the Journal of Clinical Oncology in 2021, demonstrated that 17 cycles of the anti-HER2 antibody drug-conjugate trastuzumab emtansine (T-DM1, Kadcyla, Roche) is highly useful for a large proportion of stage 1 patients, and can help them avoid alopecia when compared to paclitaxel.

The results presented at SABCS 2022 during a Spotlight Session show that HER2DX risk score was significantly associated with relapse-free interval despite the low number of events in both studies. Overall, these results show that HER2DX can reliably identify patients who might be ideal candidates for de-escalation of systemic therapy.

DAPHNe and GOM studies: confirming the HER2DX pCR score

The analysis of the HER2DX in DAPHNe and GOM studies is the result of the agreement between REVEAL GENOMICS and Dana-Farber Cancer Institute (US) and Hospital Universitario Gregorio Marañón (Spain), respectively, consisting of using the test to analyze tumor samples from 235 patients with early-stage HER2+ breast cancer from both trials.

The DAPHNe clinical trial was a single-arm prospective academic phase II trial in which patients with treatment-naïve stage II-III HER2+ breast cancer received a de-escalated neoadjuvant regimen of weekly paclitaxel for 12 cycles along with trastuzumab and pertuzumab (THP) every 3 weeks for 4 cycles. The results of this study have prompted the COMPASS-HER2-pCR study, led by ECOG-ACRIN, which aims to recruit more than 2000 patients.

The GOM study is a prospective observational study, ongoing since 2018, of consecutive patients with newly diagnosed stage I III HER 2 breast cancer candidates for 6 cycles of neoadjuvant docetaxel, carboplatin and trastuzumab (TCH) or TCH plus pertuzumab (TCHP) across 7 public hospitals in Spain.

The results presented at SABCS 2022 show that HER2DX pCR scores were found to strongly predict pCR in both trials, independently of known clinical-pathological variables and intrinsic subtype. It was also observed that the group with high pCR likelihood according to HER2DX benefited from the inclusion of pertuzumab to trastuzumab-based neoadjuvant chemotherapy, in contrast to the group with low pCR. Notably, the pCR rate of the DAPHNe group of patients with a HER2DX high pCR likelihood HER2DX result was 93%.

Overall, these results show that HER2DX pCR score can reliably identify patients who might be ideal candidates for neoadjuvant paclitaxel, trastuzumab and pertuzumab.

About HER2DX️

HER2DX️ is the world’s first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS️ since January 2022, HER2DX is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX️ is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e., tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX️ predicts:

Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low, and HER2+ breast cancer.