On October 10, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that new data for four approved medicines and three pipeline candidates in more than 15 types of cancer will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain, from Oct. 20-24 (Press release, Merck & Co, OCT 10, 2023, View Source [SID1234635811]). Presentations will feature new or updated findings from Merck’s broad portfolio of cancer medicines: KEYTRUDA, Merck’s anti-PD-1 therapy; WELIREG, Merck’s oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor; LENVIMA (lenvatinib), in collaboration with Eisai; and LYNPARZA (olaparib), in collaboration with AstraZeneca, and emphasize Merck’s commitment to improving outcomes for patients across multiple stages of cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Additionally, new data from Merck’s diverse pipeline will be shared at the congress, including from MK-1084, a KRAS G12C inhibitor being evaluated as monotherapy and in combination with KEYTRUDA; from MK-2870 (also known as SKB264), an anti-TROP2 antibody drug conjugate (ADC) being developed in collaboration with Kelun-Biotech; and from V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT) being developed in collaboration with Moderna, in combination with KEYTRUDA.

"At ESMO (Free ESMO Whitepaper) 2023, we look forward to sharing new research highlighting the breadth of our portfolio and expanding pipeline, as we pursue breakthrough innovations in oncology to address critical gaps in care for patients in need," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "Our continued efforts to treat cancer earlier and make a meaningful impact are fueled by one goal: To give those who are counting on us more effective ways to treat their cancer."

Key data from Merck’s portfolio to be presented at ESMO (Free ESMO Whitepaper) Congress 2023:

First presentation of survival data from the Phase 3 KEYNOTE-A39/EV-302 trial evaluating KEYTRUDA plus enfortumab vedotin as a first-line treatment for patients with locally advanced or metastatic urothelial carcinoma (Presentation #LBA6,) which will be featured in an ESMO (Free ESMO Whitepaper) Presidential Symposium and as part of the ESMO (Free ESMO Whitepaper) Press Briefings;
Presentation of overall survival (OS) results from the Phase 3 KEYNOTE-671 study evaluating KEYTRUDA in the perioperative setting (neoadjuvant KEYTRUDA plus chemotherapy followed by resection and adjuvant KEYTRUDA as a single agent) for resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC) (Presentation #LBA56);
First presentation of data from the Phase 3 KEYNOTE-A18 trial evaluating KEYTRUDA plus chemoradiotherapy in patients with high-risk, locally advanced cervical cancer (Presentation #LBA38);
First presentation of data from the Phase 3 KEYNOTE-756 trial evaluating KEYTRUDA plus neoadjuvant chemotherapy and adjuvant endocrine therapy in early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer (Presentation #LBA21);
First presentation of data from the Phase 3 LITESPARK-005 trial evaluating WELIREG for the treatment of patients with advanced renal cell carcinoma (aRCC) previously treated with immune checkpoint and anti-angiogenic therapies (Presentation #LBA88);
First time presentation of progression-free survival (PFS) and OS data from the Phase 3 KEYNOTE-811 trial evaluating KEYTRUDA plus trastuzumab and chemotherapy as first-line treatment for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma (Presentation #1511O);
Updated 5-year event-free survival data from the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA in combination with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment for patients with high-risk early-stage triple-negative breast cancer (TNBC) (Presentation #LBA18).
Key data from Merck’s pipeline to be presented at ESMO (Free ESMO Whitepaper) Congress 2023:

First-time safety and preliminary efficacy data for MK-1084, a KRAS G12C inhibitor, as a monotherapy in solid tumors and in combination with KEYTRUDA in NSCLC (Presentation #663P);
First presentation of data from a Phase 2 cohort of the Phase 1/2 trial evaluating MK-2870 (also known as SKB264) in previously treated metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer (Presentation #380MO);
Additional data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating V940 (mRNA-4157) in combination with KEYTRUDA as adjuvant treatment for high-risk melanoma (Presentation # LBA49).
Merck investor event

Merck will host an Oncology Investor Event to coincide with the ESMO (Free ESMO Whitepaper) Congress 2023 on Sunday, October 22, 2023, 7:00 p.m. CEST/1:00 p.m. ET, at which senior management will highlight key data presentations. The event will take place virtually and will be accessible via webcast. Investors, analysts, members of the media and the general public are invited to listen to a webcast of the presentation at: View Source;LangLocaleID=1033

Details on abstracts listed above and additional key abstracts related to Merck’s portfolio and pipeline at ESMO (Free ESMO Whitepaper) Congress 2023:

Breast cancer

SKB264 (MK-2870) in previously treated hormone receptor-positive (HR+)/ HER2-negative metastatic breast cancer (mBC): Results from a phase I/II, single-arm, basket trial. Y. Yin.

Presentation #380MO, Mini oral session – Breast cancer, metastatic

Pembrolizumab or placebo plus chemotherapy followed by pembrolizumab or placebo for early-stage TNBC: Updated EFS results from the phase 3 KEYNOTE-522 study. P. Schmid.

Presentation # LBA18, Proffered Paper session – Breast cancer, early stage

KEYNOTE-756: Phase 3 study of neoadjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo), followed by adjuvant pembro or pbo + endocrine therapy (ET) for early-stage high-risk ER+/HER2– breast cancer. F. Cardoso. (Led by Kelun-Biotech)

Presentation # LBA21, Proffered Paper session – Breast cancer, early stage

Gastrointestinal cancers

Pembrolizumab versus chemotherapy in microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): 5-year follow-up of the randomized phase 3 KEYNOTE-177 study. K. Shiu.

Presentation #LBA32, Mini oral session – Gastrointestinal tumours, lower digestive

Impact of baseline molecular alterations on the efficacy of tucatinib (TUC) plus trastuzumab (Tras) for HER2+, RAS WT metastatic CRC (mCRC) in MOUNTAINEER. J. Strickler. (Led by Seagen)

Presentation #551O, Proffered Paper session 1 – Gastrointestinal tumours, lower digestive

Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Survival results from the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-811 study. Y. Janjigian.

Presentation #1511O, Proffered Paper session 1 – Gastrointestinal tumours, upper digestive

Health-related quality of life (HRQoL) analysis from KEYNOTE-859: First-line (1L) pembrolizumab (pembro) + chemotherapy (chemo) for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. M. Lowery.

Presentation #1516P, Poster

Genitourinary cancers

EV-302/KEYNOTE-A39: Open-label, randomized phase 3 study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). T. Powles.

Presentation #LBA6, Presidential 2

Phase 2 LITESPARK-003 study of belzutifan in combination with cabozantinib for advanced clear cell renal cell carcinoma (ccRCC). T. Choueiri.

Presentation #LBA87, Proffered Paper session 2 – Genitourinary tumours, non-prostate

Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Randomized open-label phase 3 LITESPARK-005 study. L. Albiges.

Presentation #LBA88, Proffered Paper session 2 – Genitourinary tumours, non-prostate

Safety and efficacy of two doses of belzutifan in patients (pts) with advanced RCC: Results of the randomized phase 2 LITESPARK-013 study. N. Agarwal.

Presentation #1881O, Proffered Paper session 2 – Genitourinary tumours, non-prostate

Gynecologic cancers

Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: A randomized, double-blind, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. D. Lorusso.

Presentation #LBA38, Proffered Paper session 1 – Gynaecological cancers

Updated response data and analysis of progression free survival by mechanism of mismatch repair loss in endometrial cancer (EC) patients (pts) treated with pembrolizumab plus carboplatin/paclitaxel (CP) as compared to CP plus placebo (PBO) in the NRG GY018 trial. R. Eskander.

Presentation #LBA43, Mini oral session – Gynaecological cancers

Lung cancer

Overall survival in the KEYNOTE-671 study of perioperative pembrolizumab for early-stage non-small-cell lung cancer (NSCLC). J. Spicer.

Presentation #LBA56, Proffered Paper session – Non-metastatic NSCLC and other thoracic malignancies

Safety and preliminary efficacy of the KRAS G12C inhibitor MK-1084 in solid tumors and in combination with pembrolizumab in NSCLC. C. Rojas.

Presentation #663P, Poster

Melanoma

Pathologic response and exploratory analyses of neoadjuvant-adjuvant versus adjuvant pembrolizumab (PEM) for resectable stage IIIB-IV melanoma from SWOG S1801. S. Patel.

Presentation #LBA48, Proffered Paper session – Melanoma and other skin tumours

mRNA-4157 (V940) individualized neoantigen therapy + pembrolizumab vs pembrolizumab in high-risk resected melanoma: Clinical efficacy and correlates of response. J. Weber.

Presentation # LBA49, Proffered Paper session – Melanoma and other skin tumours

On October 10, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the Phase 3 KEYNOTE-671 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, as a perioperative treatment regimen for patients with resectable stage II, IIIA or IIIB (T3-4N2) non-small cell lung cancer (NSCLC) met its dual primary endpoint of overall survival (OS) (Press release, Merck & Co, OCT 10, 2023, View Source [SID1234635810]). At a pre-specified interim analysis, KEYTRUDA plus chemotherapy before surgery (neoadjuvant), followed by resection and KEYTRUDA as a single agent after surgery (adjuvant), demonstrated a statistically significant and clinically meaningful improvement in OS compared to neoadjuvant placebo plus chemotherapy followed by adjuvant placebo in these patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified. Full results from this analysis of KEYNOTE-671 will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 and shared with regulatory authorities worldwide.

"This is a significant milestone in the treatment of resectable non-small cell lung cancer, as it represents the first Phase 3 study to show a statistically significant overall survival benefit for these patients with stage II, IIIA or IIIB (T3-4N2) non-small cell lung cancer. These results build upon the previously reported event-free survival data, and demonstrate the potential for this KEYTRUDA-based regimen to help extend the lives of these patients," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "We’re excited by the progress we have made to help patients with earlier stages of non-small cell lung cancer, who are in need of additional treatment options."

As previously announced, at the first interim analysis, KEYNOTE-671 met the other one of its dual primary endpoints, event-free survival (EFS), as well as its key secondary endpoints of pathological complete response (pCR) and major pathological response (mPR). These results were presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and, based on these data, the U.S. Food and Drug Administration (FDA) has accepted Merck’s new supplemental Biologics License Application (sBLA) with a Prescription Drug User Fee Act (PDUFA), or target action, date of October 16, 2023.

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC and small cell lung cancer (SCLC) include KEYNOTE-671, KEYNOTE-091, KEYNOTE-867, KEYLYNK-012, KEYVIBE-006 and KEYLYNK-013.

About KEYNOTE-671

KEYNOTE-671 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03425643) evaluating neoadjuvant KEYTRUDA plus chemotherapy, followed by adjuvant KEYTRUDA as a single agent versus placebo plus neoadjuvant chemotherapy, followed by adjuvant placebo in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC. The trial’s dual primary endpoints are EFS and OS. Key secondary endpoints include pCR and mPR. The study enrolled 786 patients who were randomly assigned (1:1) to receive either:

KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for up to four cycles) plus chemotherapy (cisplatin [75 mg/m^2, IV; given on Day 1 of each cycle] and either gemcitabine [1000 mg/m^2, IV; given on Days 1 and 8 of each cycle) or pemetrexed [500 mg/m^2, IV; given on Day 1 of each cycle]) as neoadjuvant therapy prior to surgery, followed by KEYTRUDA (200 mg IV Q3W for up to 13 cycles) as adjuvant therapy post-surgery, or
Placebo (saline IV Q3W for up to four cycles) plus chemotherapy (cisplatin [75 mg/m^2, IV; given on Day 1 of each cycle] and either gemcitabine [1000 mg/m^2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m^2, IV; given on Day 1 of each cycle]) as neoadjuvant therapy prior to surgery, followed by placebo (saline IV Q3W for up to 13 cycles) as adjuvant therapy post-surgery.
About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 25%, which is a 21% improvement over the last five years. Improved survival rates are due, in part, to earlier detection and screening, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 5.8% of people in the U.S. who are eligible were screened for lung cancer in 2021.

On October 10, 2023 I-Mab (Nasdaq: IMAB) (the "Company"), a global biotechnology company focused on bringing highly differentiated medicines to patients around the world through the discovery, development, and commercialization of novel immunotherapies and biologics, reported multiple recent developments in TJ-L14B/ABL503, a differentiated PD-L1 x 4-1BB bispecific antibody developed in collaboration with ABL Bio (Kosdaq: 298380) (Press release, I-Mab Biopharma, OCT 10, 2023, View Source [SID1234635809]). TJ-L14B/ABL503 is designed to address tumors resistant to PD-(L)1 antibodies through its unique ability to conditionally activate 4-1BB upon binding to its target, PD-L1. I-Mab owns 50% of the global rights of TJ-L14B/ABL503.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

On September 7, 2023, TJ-L14B/ABL503 successfully obtained patent registration in eight Eurasian countries. The patent, officially named "Anti-PD-L1/Anti-4-1BB Bispecific Antibody and Its Applications," secures patent rights extending through 2039. Furthermore, this patent has already been granted in Chile, South Africa, and Japan. Patent examinations are currently underway in over 20 countries, including the U.S., China, and Europe.

TJ-L14B/ABL503 is currently being investigated in a Phase 1 dose-escalation study in patients with progressive, locally advanced or metastatic solid tumors who are relapsed or refractory following prior lines of treatment. The dose-expansion portion of the Phase 1 study is actively progressing in the U.S. and South Korea. Currently, we have observed 1 complete response (CR), 1 partial response (PR), and 2 patients who achieved an unconfirmed objective response upon recent enrollment. While preliminary efficacy signals have emerged, the maximum tolerated dose (MTD) has not yet been reached. The Company anticipates presenting the top-line Phase 1 clinical data at a major medical conference in the first half of 2024.

"We’re encouraged by these early results of TJ-L14B/ABL503 as they continue to demonstrate the potential of this highly differentiated treatment for tumor types with significant unmet need," said Raj Kannan, CEO of I-Mab. "With the success of patent registrations across multiple countries, and promising preliminary data from the Phase 1 study, we’re reaffirming the possibility for TJ-L14B/ABL503 to make a significant impact on the lives of people with cancer. We look forward to sharing more progress on the global development of TJ-L14B/ABL503."

"The clinical responses observed in the Phase 1 clinical study of TJ-L14B/ABL503, though in early stages, not only provide validation of our technology platform but also offer proof of the mechanism behind this innovative bispecific antibody," said Sanghoon Lee, CEO of ABL Bio. "We express our heartfelt gratitude to the patients who participated in the study, healthcare professionals, study investigators, and our partners for their invaluable collaboration in achieving this milestone. Concurrently, we are expediting patent filings for TJ-L14B/ABL503 to safeguard its rights and facilitate its seamless entry into the global market."

About TJ-L14B/ABL503

Being developed jointly with ABL Bio (Kosdaq: 298380, hereafter "ABL"), TJ-L14B/ABL503 is a differentiated PD-L1-based bispecific antibody with the PD-L1 arm as the tumor-dependent T-cell activator and the 4-1BB arm as the conditional T cell activator upon tumor engagement. Using ABL’s "Grabody-T" bispecific antibody platform technology, TJ-L14B/ABL503 stimulates 4-1BB activation only in the presence of PD-L1 expressing tumor cells to minimize the risk of off-tumor toxicity. Preclinical studies have demonstrated that the bispecific antibody shows better anti-tumor activity than equimolar doses of single agents alone or in combination. A Phase 1 study is currently being conducted in the U.S. and South Korea.

On October 10, 2023 Helsinn Group ("Helsinn"), a fully integrated, global biopharma company with a track record of over forty years of commercial execution and a strong focus in supportive care, oncology, and rare diseases, reported the signing of a new financing agreement with BancaStato, effective from September 2023 (Press release, Helsinn, OCT 10, 2023, View Source [SID1234635808]).
This financing agreement with BancaStato replaces Helsinn’s prior credit facility agreement signed by Helsinn with a non-bank lender in December 2022. This new funding agreement offers convenient terms and conditions which will help drive the Company’s business objectives.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Helsinn has recently undergone a strategic review to redefine its business model, activities, and investments to remain competitive in global markets. Proceeds from the recently concluded financing agreement will contribute to the implementation of the Company’s plans and will help to ensure sustainable and profitable performance in alignment with the current product portfolio as well as commercial and manufacturing capabilities – the company’s main pillars of success in the past.

Riccardo Braglia, Executive Chairman of Helsinn, commented: "Guided by our core values of respect, integrity, and quality, Helsinn’s strategy focuses on being the partner of choice as a commercial-stage enterprise with a strong focus in supportive care, oncology and rare diseases, able to reach patients worldwide through integrated CMC/manufacturing/supply and a commercial platform complemented by scientific and technological expertise.
We are very grateful to BancaStato for placing their trust in our business model and our solid commercial track record."

Dr. Melanie Rolli, Chief Executive Officer at Helsinn, said: "This new financial strength from BancaStato is a great step forward which will allow us to reach our business objectives as well as strengthen our portfolio of late- and commercial-stage supportive care, oncology and rare disease drugs and, more importantly, to continue to serve our customers around the world by identifying and collaborating with partners who share our passion and motivation: to extend and improve the lives of patients globally who use our products every day."

On October 10, 2023 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines, reported that the Compensation Committee of the company’s Board of Directors granted three employees nonqualified stock options to purchase an aggregate of 47,000 shares of its common stock with an exercise price of $2.41, which is equal to the closing price of Gritstone’s common stock on October 5, 2023, the date of the grant (Press release, Gritstone Bio, OCT 10, 2023, View Source [SID1234635807]). These stock options are part of an inducement material to the new employees becoming an employee of Gritstone, in accordance with Nasdaq Listing Rule 5635(c)(4).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

The stock options will vest over a four-year period, with 25% of the options vesting on the first anniversary of the employees’ date of hire, and 1/48th of the options vesting monthly thereafter, subject to the employees’ continued employment with Gritstone on such vesting dates. The stock options are subject to the terms and conditions of Gritstone’s 2021 Employment Inducement Incentive Award Plan and the stock option agreement covering the grant.