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Flamingo Therapeutics Announces Poster Presentation at ESMO Congress 2023

On October 17, 2023 Flamingo Therapeutics ("Flamingo") reported the presentation of a "Trials-in-Progress", or TiP, poster at the ESMO (Free ESMO Whitepaper) Congress 2023, taking place October 20-24, 2023, in Madrid, Spain (Press release, Flamingo Therapeutics, OCT 17, 2023, View Source;utm_medium=rss&utm_campaign=flamingo-therapeutics-announces-poster-presentation-at-esmo-congress-2023 [SID1234636063]). Members of the Flamingo leadership team, Andrew Denker, MD, PhD, Chief Medical Officer, and Morgane Perdomini, PhD, Director Development, will be present at the congress.

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Details of the TiP poster presentation are below:

Title: "PEMDA-HN, an Open-Label, Phase II, Randomized Controlled Study of Danvatirsen Plus Pembrolizumab Compared to Pembrolizumab Alone in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC)"

Presentation #: 943 TiP

Date: Sunday, October 22, 2023

Presenting Author: Nabil F. Saba (Atlanta, United States of America)

More details can be found on the ESMO (Free ESMO Whitepaper) website.

Elevar Therapeutics and Jiangsu Hengrui Pharma Announce Global Commercialization Licensing Agreement for PD-1 Inhibitor Camrelizumab in Combination with Rivoceranib for uHCC

On October 17, 2023 Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd. and fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, and Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma), one of China’s largest pharmaceutical companies, reported a global licensing agreement that grants Elevar rights to commercialize and develop Hengrui Pharma’s anti-PD-1 antibody camrelizumab in combination with rivoceranib for unresectable hepatocellular carcinoma (uHCC) worldwide, excluding Greater China Region and Korea (Press release, Elevar Therapeutics, OCT 17, 2023, View Source [SID1234636062]).

Under the terms of the agreement, Elevar will pay Hengrui Pharma up to $600 million of sales milestones and a double-digit percentage royalty on camrelizumab net sales. The total estimated 10-year payout could be up to $1 billion.

In May 2023, a new drug application (NDA) for rivoceranib and a biologics license application (BLA) for camrelizumab were submitted to the U.S. Food and Drug Administration (FDA) for the combination of rivoceranib and camrelizumab as a first-line therapy for uHCC. The FDA accepted the submissions, assigning Prescription Drug User Fee Act (PDUFA) target action dates in May 2024.

Rivoceranib is developed by Hengrui Pharma in China. In January 2023, the combination was approved in China as a first-line treatment for uHCC. Elevar maintains development rights to rivoceranib outside of China and Korea.

"This agreement will boost our companies’ shared focus on advancing the standard of care in uHCC, as having both camrelizumab and rivoceranib under one portfolio will significantly streamline commercialization," said Saeho Chong, Elevar chief executive officer. "In our investigational Phase 3 CARES-310 study, the combination was shown to provide the highest reported median overall survival of any currently available uHCC treatment. Elevar’s alliance with Hengrui Pharma is a catalyst for our world-class team as we focus on bringing life-changing products to cancer patients."

Each year, liver cancer is the cause of more than 830,000 deaths worldwide1. HCC is the most common type of liver cancer and typically has a poor prognosis with a lack of treatment options.

With 14 research and development centers built around the world and several subsidiaries established in the U.S., EU, Australia and Japan, Hengrui Pharma is globally focused on innovation and open collaboration. The company has 13 in-house-developed innovative products and two in-licensed innovative products marketed in China, more than 80 proprietary innovative candidates in the R&D stage and nearly 20 under clinical development worldwide.

Hengrui has also demonstrated a clear commitment to HCC patients globally, as its initial efforts in China led to the 2020 approval of rivoceranib, under the name Aitan, as a single agent for a second-line treatment for advanced HCC.

Elevar and Hengrui Pharma first shared results for the CARES-310 study in September 2022 at the annual Congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper). The results were also published in The Lancet on July 24, 2023. Camrelizumab plus rivoceranib significantly prolonged overall survival and progression-free survival, and increased overall response rate versus sorafenib, a standard first-line treatment for uHCC.

About Hepatocellular Carcinoma (HCC)
HCC is the most common type of primary liver cancer. It most frequently occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC typically has a poor prognosis and a lack of treatment options and is therefore a condition with an urgent medical need.

About Camrelizumab
Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1). Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Currently, more than 10 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer) and treatment settings.

Camrelizumab, under the brand name AiRuiKa, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma, nasopharyngeal carcinoma in the first-line setting, and uHCC in combination with rivoceranib as a first-line treatment. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021.

About Rivoceranib
Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression.

Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf). Rivoceranib was the first TKI approved in gastric cancer in China (2014). It is also approved in China as a single agent for a second-line treatment for advanced HCC (2020) and in combination with camrelizumab for a first-line treatment for uHCC (2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.).

Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan.

Delivery Of Encapsulated Accutoxtm-Chitosan Nanoparticles Triggers Complete Tumor Regression In Animals With Pre-Estabslihed Solid Lymphoma

On October 17, 2023 Defence Therapeutics Inc. ("Defence" or the "Company"), a Canadian biopharmaceutical company specialized in the development of immune-oncology vaccines and drug delivery technologies, reported that systemic administration of novel AccuTOXTM-chitosan encapsulated formulation inhibits the growth of pre-established solid lymphoma resulting in their progressive shrinking overtime (Press release, Defence Therapeutics, OCT 17, 2023, View Source;utm_medium=rss&utm_campaign=delivery-of-encapsulated-accutoxtm-chitosan-nanoparticles-triggers-complete-tumor-regression-in-animals-with-pre-estabslihed-solid-lymphoma [SID1234636061]).

The conducted study had two main objectives: i) to test whether AccuTOXTM can be delivered systemically if encapsulated in chitosan-based nanoparticles, and ii) to assess whether this modality can synergize with immune-checkpoint blockers commonly used in the oncology clinic. The formulation was delivered twice with a 2 weeks interval and treated animals were followed for up to 40 days. The tumors in animals treated with AccuTOXTM-Chitosan injections along with anti-PD-1 co-administration regressed and exhibited a prolonged survival rate.

"The AccuTOXTM molecule can be toxic if delivered unconjugated and/or systemically. The Defence team was able to bypass this limitation by encapsulating it into chitosan-based nanoparticles. This is a simpler and cheaper method compared to the use of antibodies, and may represent a key component of Defence’s future encapsulation strategies", says Mr. Plouffe, CEO of Defence Therapeutics.

Chitosan is a linear polysaccharide composed of randomly distributed β-(1→4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit), and has a number of commercial and biomedical uses. In addition to its agricultural and industrial applications, chitosan is often useful in bandages to reduce bleeding and as an antibacterial agent. It can also be used to help deliver drugs through the skin. Therefore, exploiting it as a delivery vehicle for unconjugated Accum or its variants could revolutionize the future of molecular medicine by increasing the compounds specificity to tumor site while minimizing the needed dosage and thus, associated side effects.

CytoAgents Announces Initiation of Patient Enrollment in Phase 1b/2a Clinical Trial to Treat Cytokine Release Syndrome in CAR T-cell Therapy

On October 17, 2023 CytoAgents, Inc., a clinical-stage biotechnology company developing a safe, effective treatment for Cytokine Release Syndrome (CRS), reported that it has initiated recruitment and will enroll its first patient at UPMC Hillman Cancer Center, in the Phase 1b/2a clinical trial evaluating the therapeutic, CTO1681, to treat CRS in lymphoma patients receiving CAR T-cell Therapy (Press release, CytoAgents, OCT 17, 2023, View Source [SID1234636060]).

"This clinical trial (CTA-2101) addresses an area of great unmet medical need as the majority of patients receiving CAR T-cell Therapy experience the toxicities of CRS and associated neurotoxicity," said Arthur P. Bertolino, MD, PhD, MBA, Chief Medical Officer at CytoAgents.

The clinical trial will be conducted at multiple U.S. sites, with UPMC Hillman Cancer Center now the initial enrolling site. The trial investigates the safety, tolerability, and efficacy of different doses of CTO1681 in lymphoma patients receiving CAR T-cell therapy.

"We were early adopters of CAR T-cell therapy and remain committed to providing this treatment for our patients in the safest way possible," said Robert L. Ferris, M.D., Ph.D., a physician-scientist, and director of UPMC Hillman Cancer Center. "We are dedicated to solving the CRS problem associated with CAR T-cell therapy and to be a part of this clinical trial at our institution."

CytoAgents is developing innovative pharmaceutical products to treat life-threatening conditions, diseases and disorders associated with CRS, commonly referred to as cytokine storm. CRS is caused by excessive cytokine production and can be triggered by a range of diseases and treatments. Certain advanced immunotherapies in the oncology space such as CAR T-cell and Bispecific Antibody Therapies suffer from high incidence of associated CRS. The company expects that effective CRS management will support greater accessibility to and broader adoption of these highly effective therapies in the clinic.

"We are thrilled to advance CTO1681 into the clinic to establish key insights into the safety and efficacy of our novel therapeutic," said Teresa Whalen, RPh, CEO at CytoAgents. "Dosing our first patients in the lymphoma population is an important step forward for the company and the patients who may benefit. We look forward to continued enrollment with data anticipated in 2024."

Details of the CTA-2101 trial can be found at www.clinicaltrials.gov under the identifier NCT05905328.

Neoadjuvant Opdivo (nivolumab) with Chemotherapy Provides Benefits for Patients with Resectable Non-Small Cell Lung Cancer Across PD-L1 Expression Levels with Three-Year Follow Up in CheckMate -816 Trial

On October 17, 2023 Bristol Myers Squibb (NYSE: BMY) reported three-year follow-up results from exploratory analyses of the Phase 3 CheckMate -816 trial, demonstrating sustained event-free survival (EFS) and promising overall survival (OS) trends with three cycles of Opdivo (nivolumab) in combination with platinum-based chemotherapy for the neoadjuvant treatment of patients with resectable non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels (Press release, Bristol-Myers Squibb, OCT 17, 2023, View Source;816-Trial/default.aspx [SID1234636059]). Neoadjuvant Opdivo with chemotherapy also showed improvements in pathologic complete response (pCR) and major pathologic response (MPR) over chemotherapy alone in PD-L1 ≥1% and <1% patient populations. The safety profile of the Opdivo-based regimen was consistent across all PD-L1 subgroups. These results will be featured in a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 on October 23, 2023, from 8:45 a.m. to 9:55 a.m. EDT / 14:45 to 15:55 CEST (Abstract #LBA57).

"The three-year results with neoadjuvant nivolumab with chemotherapy are a continuation of the statistically significant and clinically meaningful results we have seen with this regimen in the treatment of resectable non-small cell lung cancer, and they provide hope for patients that they may achieve long-term benefit," said Mariano Provencio Pulla, M.D., Ph.D., Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain. "It is encouraging to see that this neoadjuvant immunotherapy combination has demonstrated improvements across efficacy measures, regardless of PD-L1 expression levels, including within the PD-L1 negative subgroup that faces high unmet needs and represents approximately 40% of the study population. The CheckMate -816 data clearly indicate the potential for better outcomes for patients with this regimen than chemotherapy alone."

With a median follow-up of 41.4 months in the CheckMate -816 trial, exploratory analyses showed:

OS: While OS remains immature at this follow-up, promising OS trends were seen in both PD-L1 ≥1% and <1% patient populations. For patients with tumor PD-L1 expression ≥1%, Opdivo with chemotherapy reduced the risk of death by 63% (Hazard Ratio [HR] 0.37; 95% Confidence Interval [CI]: 0.20 to 0.71). Three-year OS rates favored neoadjuvant Opdivo with chemotherapy over chemotherapy alone at 85% vs. 66%, respectively. In patients with PD-L1 <1%, Opdivo with chemotherapy reduced the risk of death by 19% (HR 0.81; 95% CI: 0.48 to 1.36), with three-year OS rates being 71% vs. 60%.
EFS: Among patients with tumor PD-L1 expression ≥1%, three-year EFS rates were 72% with neoadjuvant Opdivo with chemotherapy vs. 47% with chemotherapy alone (HR 0.46; 95% CI: 0.28 to 0.77). In patients with tumor PD-L1 expression <1%, EFS rates were 42% with the combination vs. 39% with chemotherapy (HR 0.87; 95% CI: 0.57 to 1.35).
pCR: In patients with PD-L1 ≥1%, pCR rates were 32.6% with neoadjuvant Opdivo with chemotherapy compared to 2.2% with chemotherapy alone. For those with PD-L1 <1%, pCR rates were 16.7% vs. 2.6%, respectively.
MPR: Among patients with PD-L1 ≥1%, MPR rates with neoadjuvant Opdivo with chemotherapy were 44.9% vs. 5.6% with chemotherapy. For patients with PD-L1 <1%, MPR rates were 29.5% with the Opdivo-based regimen and 14.3% with chemotherapy alone.
Definitive Surgery: Definitive surgery rates with Opdivo with chemotherapy vs. chemotherapy were 84% vs. 74% in patients with tumor PD-L1 expression ≥1% and 81% vs. 77% in patients with tumor PD-L1 expression <1%. Of these, complete resection was achieved in 91% vs. 82% and 79% vs. 76% of cases, respectively.
"At ESMO (Free ESMO Whitepaper) this year, we are presenting data from several trials across stages and treatment settings in non-small cell lung cancer, including two studies in resectable disease. This is an area of research that we are heavily committed to, as it presents an important opportunity to treat cancer at earlier stages when the tumor is most responsive to treatment and the patient’s immune system is most intact," said Abderrahim Oukessou, M.D., vice president, thoracic cancers global program lead, Bristol Myers Squibb. "We are thrilled to see consistent results with the neoadjuvant regimen of Opdivo with chemotherapy from the CheckMate -816 study, regardless of PD-L1 expression, which build on the benefits we have already seen that led to multiple approvals of this combination globally. We want to sincerely thank every patient and investigator involved in the clinical trial."

Opdivo and Opdivo-based combinations have shown improved efficacy in the neoadjuvant, adjuvant or perioperative treatment of four earlier-stage tumor types, including lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer and melanoma.

About CheckMate -816

CheckMate -816 is a Phase 3 randomized, open label, multi-center trial evaluating Opdivo with chemotherapy compared to chemotherapy alone as neoadjuvant treatment in patients with resectable stage IB to IIIA non-small cell lung cancer (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control staging criteria), regardless of PD-L1 expression. For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy every three weeks for three cycles, or platinum doublet chemotherapy every three weeks for three cycles, followed by surgery. The primary endpoints of the trial are event-free survival and pathologic complete response. Secondary endpoints include overall survival, major pathologic response, and time to death or distant metastases.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Non-metastatic cases account for the majority of NSCLC diagnoses (approximately 60%, with up to half of these being resectable), and the proportion is expected to grow over time with enhanced screening programs. While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes.