Folinic Acid

The top-line data also saw statistically significant and clinically meaningful improvement in overall survival (OS). Credit: Shutterstock / NMK-Studio. Pfizer ’s metastatic colorectal cancer (mCRC) combination therapy has met one of the primary endpoints of improving progression-free survival (PFS) in a Phase III trial, further supporting a full approval. The company’s active-controlled, open-label BREAKWATER trial (NCT05217446) evaluating a combination of Pfizer’s Braftovi (encorafenib), Eli Lilly’s Erbitux (cetuximab) and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) met one of its dual primary endpoints, improving PFS. The trial investigated the combination in mCRC patients living with a BRAF V600E mutation who are treatment-naive. The top-line data also saw statistically significant and clinically meaningful improvement in overall survival (OS). Additionally, the company has added that no new safety signals have been observed. In December 2024, the US Food and Drug Administration (FDA) granted accelerated approval to the combination therapy of Braftovi, Erbitux and mFOLFOX6. Although it is waiting on full analysis of the final results, Pfizer intends to present its findings in a meeting with the FDA to support full approval. Speaking ahead of World Cancer Day on 4 February, Pfizer’s chief oncology officer Roger Dansey said: “We are extremely pleased with the clinically meaningful PFS and OS results from the BREAKWATER study, which have the potential to be practice-changing for this patient population that has historically had limited treatment options and poor outcomes. “The Braftovi regimen is emerging as a new standard of care as the first targeted therapy approved for use as early as first-line for patients with mCRC with a BRAF V600E mutation.” The multi-centre BREAKWATER trial is also the first trial to be launched under the regulatory body’s Project FrontRunner, an initiative aimed at encouraging sponsors to seek approval for drugs for patients in an earlier stage of clinical treatment. This is as opposed to seeking approval for treatments designed for patients who have already undergone several therapies or treatment options. In the BREAKWATER trial patients were randomised to receive either 300mg of Braftovi and Erbitux alone or in combination with mFOLFOX6. The active control group received mFOLFOX6, FOLFOXIRI (Folinic acid, fluorouracil, oxaliplatin and irinotecan), or CAPOX (capecitabine and oxaliplatin) with or without bevacizumab. A BRAF mutation is a form of cancer in which the BRAF gene begins to cause certain cells to continue dividing without ever receiving a signal to stop. The V600E variant is one of the more common forms of BRAF mutation with the name defining the location and nature of the condition. While some BRAF mutations are susceptible to different forms of targeted therapy, other BRAF mutations are not. Elsewhere in the treatment of mCRC, Tizona Therapeutics has expanded its ongoing Phase Ib clinical trial of TTX-080, a novel antibody targeting human leukocyte antigen-G (HLA-G), in patients with the condition. Meanwhile, Johnson & Johnson has reported a 49% overall response rate in a colorectal cancer study with RYBREVANT.

LEXINGTON, Mass.--( BUSINESS WIRE )--Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology, today announced 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 Gastrointestinal Cancers (ASCO GI) Symposium. The conference will take place on January 23-25, 2025, in San Francisco, California. 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 21 st , 2025. Data presented at the conference will be available to view in the publications section of the Agenus website ( https://agenusbio.com/publications ) following the ASCO GI Meeting. *Agenus Sponsored Study About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. About Botensilimab (BOT) Botensilimab (BOT) is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Approximately 1,100 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2023, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.