On December 18, 2024 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology, reported five presentations featuring botensilimab (BOT, an Fc-enhanced anti-CTLA-4 antibody) plus balstilimab (BAL, an anti-PD-1 antibody) at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers (ASCO GI) Symposium (Press release, Agenus, DEC 18, 2024, View Source [SID1234649207]). The conference will take place on January 23-25, 2025, in San Francisco, California.

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The presentations will showcase BOT/BAL’s activity across three distinct colorectal cancer settings—late-line metastatic, first-line, and neoadjuvant treatment. The studies demonstrate BOT/BAL’s consistent activity in microsatellite stable (MSS) colorectal cancer (CRC), which accounts for over 80% of CRC cases and has limited treatment options, as well as its efficacy in microsatellite instability-high (MSI-H) CRC. Additionally, one presentation will feature BOT/BAL and invariant natural killer T cells (iNKTs) in patients with refractory gastric cancer.

"These presentations will highlight BOT/BAL’s potential to benefit patients across colorectal cancer treatment settings, including the neoadjuvant, late-line, and first-line settings," said Dr. Garo Armen, Chairman and CEO of Agenus. "We aim to transform outcomes at every stage of disease and deliver renewed hope for patients worldwide."

Presentation Details

Abstract Title: Preliminary results from a randomized, open-label, phase 2 study of botensilimab (BOT) with or without balstilimab (BAL) in refractory microsatellite stable metastatic colorectal cancer with no liver metastases (MSS mCRC NLM)*
Abstract Number: 23
Presenting Author: Dr. Marwan Fakih
Session: Rapid Oral Abstract Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 9:15 AM-10:00 AM PST

Abstract Title: Preoperative botensilimab (BOT) with or without balstilimab (BAL) for patients with resectable locally advanced pMMR or dMMR colon cancer: Results from the UNICORN trial by GONO
Abstract Number: 158
Presenting Author: Dr. Filippo Ghelardi
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 7:00 AM-7:55 AM PST

Abstract Title: A phase II study of agenT-797 (invariant natural killer T-cells), botensilimab (Fc-enhanced CTLA-4 inhibitor) and balstilimab (anti-PD-1) in patients with advanced, refractory gastroesophageal adenocarcinoma
Abstract Number: TPS515
Presenting Author: Dr. Samuel Cytryn
Session: Trials in Progress Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Session Date and Time: 1/23/2025, 11:30 AM-1:00 PM PST

Abstract Title: Neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable mismatch repair proficient (pMMR) and deficient (dMMR) colorectal cancer (CRC): NEST clinical trial update
Abstract Number: 207
Presenting Author: Dr. Erika Hissong
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 7:00 AM-7:55 AM PST

Abstract Title: A phase 1 trial of folinic acid, fluorouracil, oxaliplatin, bevacizumab, botensilimab, balstilimab (FOLFOX-3B) in microsatellite stable metastatic colorectal cancer.
Abstract Number: 180
Presenting Author: Dr. Marwan Fakih
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 7:00 AM-7:55 AM PST

Complete abstracts will be released at 5:00 PM ET on January 21st, 2025. Data presented at the conference will be available to view in the publications section of the Agenus website (View Source) following the ASCO (Free ASCO Whitepaper) GI Meeting.

On December 18, 2024 ALX Oncology Holdings Inc. ("ALX Oncology" or "the Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives, reported that the updated results from its Phase 2 ASPEN-06 clinical trial have been accepted for oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, which will be held in San Francisco from January 23 – 25, 2025 (Press release, ALX Oncology, DEC 18, 2024, View Source [SID1234649192]).

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ASPEN-06 is a randomized, multi-center, international trial (NCT05002127) evaluating evorpacept, ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated proprietary Fc domain, in combination with trastuzumab, CYRAMZA (ramucirumab) and paclitaxel (collectively, TRP) against TRP alone for the treatment of patients with HER2-positive gastric/gastroesophageal junction cancer, where all patients had received an anti-HER2 agent in prior lines of therapy.

The updated results from the ASPEN-06 study will be detailed in the following oral presentation:

Title: Final analysis of the randomized phase 2 part of the ASPEN-06 study: A phase 2/3 study of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with HER2-overexpressing gastric/gastroesophageal cancer (GC)
Abstract Number: 332
Presenter: Kohei Shitara, MD, Director of the Department of Gastrointestinal Oncology, at National Cancer Center Hospital East, Kashiwa in Japan
Presentation Date and Time: Thursday, January 23, 2025, from 9:15 a.m. – 10:00 a.m. PST
Session Information: Rapid Oral Abstract Session A: Cancers of the Esophagus and Stomach
Location: Level 2 Ballroom

Copies of the presentations will be available on the Publications section of ALX Oncology’s website following presentation at the meeting.

On December 18, 2024 Sprint Bioscience AB (publ) reported that the company is broadening its portfolio with a drug development program for the treatment of acute myeloid leukemia (AML). The program targets the decapping scavenger enzyme (DCPS), a target protein that has been validated both in scientific literature and by Sprint Bioscience in collaboration with Associate Professor Julian Walfridsson at Karolinska Institutet.

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The initiation of Sprint Bioscience’s DCPS program is part of the company’s strategy to capitalize on its platform for small-molecule drug discovery to broaden the portfolio in the cancer area and to bring more opportunities for future licensing deals.

The DCPS program focuses on a target protein that degrades a metabolite resulting from the processing of mRNA. Both small-molecule inhibition and genetic knock-down of DCPS affects the differentiation and proliferation of several AML cell lines as well as patient-derived samples. Furthermore, healthy tissue seems to be insensitive to DCPS inhibition, indicating that DCPS inhibitors could offer a safe and effective treatment option for AML patients. Sprint Bioscience has also identified biomarkers to predict response to DCPS inhibition, enabling patient selection and clinical success for patients with unmet therapeutic needs.

"We have identified a target protein that constitutes a very attractive approach for the treatment of AML. We aim to advance the project to a stage where it can be licensed to an international pharmaceutical company, enabling further clinical development and progression towards the market to benefit AML patients in need of new treatment options," said, Johan Emilsson, CEO of Sprint Bioscience.

AML is a severe type of blood cancer. The Global Burden of Disease study estimates that about 140,000 people around the world are diagnosed with AML on a yearly basis. There is an urgent medical need to identify safe and effective therapies to improve treatment outcomes.

Sprint Bioscience’s portfolio now consists of six internal drug development programs (five of which are in cancer) and one program that has been licensed to Day One Biopharmaceuticals.

(Press release, Sprint Bioscience, DEC 18, 2024, View Source [SID1234660961])

On December 18, 2024 Break Through Cancer reported to have launched a collaborative cohort for a Phase 1 study of RMC-6236, a compound developed by Revolution Medicines that is designed to suppress multiple RAS proteins that drive human cancers, including pancreatic cancer, non-small cell lung cancer and colorectal cancer (Press release, Break Through Cancer, DEC 18, 2024, View Source;utm_medium=rss&utm_campaign=collaboration-with-revolution-medicines-to-study-biomarkers-for-rason-multi-selective-inhibitor-in-pancreatic-cancer [SID1234649193]).

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The ongoing phase 1 trial of RMC-6236 (NCT05379985) is exploring the safety, tolerability and antitumor activity of RMC-6236 in patients with common KRAS mutations (including G12D, G12V and G12R) in metastatic pancreatic ductal adenocarcinoma (PDAC)— the most common and highly aggressive type of pancreatic cancer, with an average 5-year survival rate of only 3% for metastatic cases. Patient blood and tumor tissue samples from a dedicated collaboration cohort within this trial will be analyzed by The Conquering KRAS in Pancreatic Cancer TeamLab, funded jointly by Break Through Cancer and the Lustgarten Foundation, using advanced multi-omic and spatial profiling approaches to search for biomarkers able to predict tumor response and how cancer cells adapt to the therapy. Such biomarkers are being studied to help doctors quickly know if a patient is or is not responding to a therapy, and whether they would benefit from combination therapies.

Beyond assessing patient outcomes, the trial is uniquely designed to deepen the understanding of the biology of KRAS-mutant pancreatic cancers. By studying patient samples and biopsies in the lab, researchers will use advanced technologies to explore how PDAC evolves under treatment, the biological impact of RAS inhibition, and the mechanisms underlying resistance. This comprehensive approach will provide critical insights into the complex interplay of tumor biology and drug response.

Cancer-causing RAS proteins drive a significant number of all human cancers, including over 90% of PDAC, and many KRAS G12 mutations in particular are prevalent in human cancers. Many KRAS-targeted cancer therapies target only single KRAS mutations, while RMC-6236 was designed to inhibit the full spectrum of cancer-causing KRAS mutations, as well as other cancer-causing RAS family member mutations as well.

"We’re delighted to have the opportunity to work with Break Through Cancer and the Lustgarten Foundation on this unique cohort within our Phase 1 study for RMC-6236," said Wei Lin, M.D., Chief Medical Officer at Revolution Medicines. "The funded investigators at Break Through Cancer will use the latest scientific techniques to examine the biological effects of RMC-6236 on pancreatic tumors in patients in our clinical trial. We hope to glean insights into the mechanisms of response and resistance to RMC-6236, which will guide us to develop potential combination therapies based on our RAS(ON) inhibitors to improve patient outcomes."

The multi-center trial is being conducted by Revolution Medicines with clinical investigators at Break Through Cancer participating institutions, including Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, The University of Texas MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center. The work is powered by Break Through Cancer’s TeamLab model of "radical collaboration," which enables real-time data and discovery sharing in laboratories across these clinical sites and in MIT’s Koch Institute for Integrative Cancer Research. Alongside this trial, TeamLab members are also investigating mechanisms of resistance to RMC-6236 and are searching for additional signaling pathways that could be promising targets for future therapeutics.

"Our mission is to drive innovation through collaboration, and this trial represents an extraordinary opportunity to do just that," said Tyler Jacks, president of Break Through Cancer; founding director of MIT’s Koch Institute for Integrative Cancer Research; David H. Koch (1962) Professor of Biology. "Together with Revolution Medicines and our TeamLab investigators, we’re applying advanced technologies and multi-institutional expertise to tackle one of the toughest challenges in oncology – pancreatic cancer.

On December 18, 2024 Coherus BioSciences, Inc. ("Coherus," NASDAQ: CHRS) reported that an abstract highlighting final clinical and biomarker data from its Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-antagonistic antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC), has been selected for a poster presentation at the upcoming 2025 ASCO (Free ASCO Whitepaper) GI Annual Meeting, being held January 23-25, 2025, in San Fransisco, CA (Press release, Coherus Biosciences, DEC 18, 2024, View Source [SID1234649194]).

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"Casdozo is a first-in-class antibody, and in oncology, is the first IL-27 cytokine antagonist to demonstrate monotherapy responses and immune activation with a safety profile that lends itself to combination," said Rosh Dias, M.D., Coherus’ Chief Medical Officer. "We look forward to sharing the final data from this Phase 2 combination study of casdozo with standard of care with the medical community at the upcoming 2025 ASCO (Free ASCO Whitepaper)-GI annual meeting. We now have data across several tumor types for casdozo demonstrating clinical activity. We are particularly excited about HCC given the strong preclinical package for targeting IL-27 in liver cancer and now translation to the clinic."

Coherus has initiated a new randomized Phase 2 study (NCT06679985) evaluating casdozo, in combination with bevacizumab and toripalimab, Coherus’ next-generation anti-PD-1 monoclonal antibody, in participants with first-line HCC. This randomized, parallel, open-label Phase 2 study is designed to evaluate the safety, efficacy, and Project Optimus1 dosing of the triplet combination. The study is expected to enroll up to 72 patients, who will be randomized to receive one of two biologically active doses of casdozo with toripalimab plus bevacizumab or toripalimab plus bevacizumab without casdozo.

"Advancing casdozo development in first-line HCC with a randomized Phase 2 combination study marks a significant milestone in our strategic path to progress our clinical pipeline, which is focused on overcoming immune suppression in the tumor microenvironment to extend survival and improve outcomes for patients and pursuing new indications for toripalimab in the U.S.," continued Dr. Dias. "Casdozo has shown encouraging responses in the first line setting when added to the existing standard of care, atezolizumab and bevacizumab, and we’re excited to build upon these data with this new Phase 2 study evaluating casdozo in combination with toripalimab and bevacizumab."

In the Phase 3 HEPATORCH study, conducted by Junshi Biosciences, patients with advanced HCC treated with toripalimab combined with bevacizumab as a first-line therapy showed significantly better clinical efficacy than sorafenib monotherapy.2 HEPATORCH patients showed an objective response rate of 25.3% versus 6.1% in the sorafenib group, a median progression-free survival of 5.8 months, and a median overall survival of 20 months, compared to 4 and 14.5 months, respectively, for the sorafenib group.3 Toripalimab in combination with bevacizumab was well tolerated, with a toxicity profile consistent with the known toxicity profile of each monotherapy, with no new safety signals identified.3 The results of the HEPATORCH study support the clinical study of toripalimab in combination with bevacizumab as a new first-line treatment option for advanced HCC which, along with the results from the Phase 2 casdozo study reported to date, support pursuing a triple combination of casdozo with toripalimab plus bevacizumab in patients with advanced or metastatic HCC.

ASCO-GI 2025 Presentation Details

Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC)
Lead Author: Daneng Li, City of Hope National Comprehensive Cancer Center
Abstract #: 605
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Date and Time: Friday, January 24, 2025; 11:30 a.m. – 1:00 p.m. PT

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma; HCC), gall bladder, and bile ducts (collectively called biliary tract cancers). The most common type of primary liver cancer in adults is HCC (accounting for ~90%), which is the third leading cause of cancer-related deaths worldwide. According to the NCI Surveillance, Epidemiology and End Results Program (SEER), there will be an estimated 41,630 new cases and 29,840 deaths from liver and intrahepatic bile duct cancer in the US in 2024.4 The U.S. 5-year relative survival rate for liver and intrahepatic bile duct cancer is 21.7%.4 The liver cancer treatment pattern has changed in recent years with the emergence of immunotherapy combinations and will continue to evolve as more treatment options become available for these highly lethal cancers.