Agenus Presents Data at ASCO GI Demonstrating Impact of BOT/BAL in Colorectal Cancer Across Neoadjuvant and Advanced Disease
Agenus (NASDAQ: AGEN) presented new data on botensilimab (BOT) and balstilimab (BAL) combination therapy at ASCO GI, demonstrating significant potential in colorectal cancer (CRC) treatment. The data comes from multiple studies involving over 1,100 patients across 60+ centers worldwide.
Key findings include results from two neoadjuvant studies (UNICORN and NEST) with 80+ patients, showing promising pathological complete response rates: 93% in dMMR/MSI-H tumors and 29% in pMMR/MSS tumors. In first-line treatment, the combination with FOLFOX-Bevacizumab achieved 71% overall response rate in 14 patients.
A global Phase 2 study with 234 patients demonstrated 19% overall response rate and 55% disease control rate in refractory MSS mCRC, with 70% of responses ongoing at data cut-off. The therapy showed particular promise in treating microsatellite stable (MSS) CRC tumors, which represent 85-95% of CRC cases and typically don't respond to immunotherapy.
Agenus (NASDAQ: AGEN) ha presentato nuovi dati sulla terapia combinata con botensilimab (BOT) e balstilimab (BAL) all'ASCO GI, dimostrando un potenziale significativo nel trattamento del cancro colorettale (CRC). I dati provengono da diversi studi che coinvolgono oltre 1.100 pazienti in più di 60 centri in tutto il mondo.
I principali risultati includono i dati di due studi neoadiuvanti (UNICORN e NEST) con oltre 80 pazienti, mostrando tassi promettenti di risposta completa patologica: 93% nei tumori dMMR/MSI-H e 29% nei tumori pMMR/MSS. Nel trattamento di prima linea, la combinazione con FOLFOX-Bevacizumab ha raggiunto un tasso di risposta globale del 71% in 14 pazienti.
Uno studio globale di Fase 2 con 234 pazienti ha dimostrato un tasso di risposta globale del 19% e un tasso di controllo della malattia del 55% nel mCRC MSS refrattario, con il 70% delle risposte ancora in corso al momento della raccolta dei dati. La terapia ha mostrato particolare promessa nel trattamento dei tumori CRC microsatellite stabili (MSS), che rappresentano l'85-95% dei casi di CRC e tipicamente non rispondono all'immunoterapia.
Agenus (NASDAQ: AGEN) presentó nuevos datos sobre la terapia combinada con botensilimab (BOT) y balstilimab (BAL) en ASCO GI, demostrando un potencial significativo en el tratamiento del cáncer colorrectal (CRC). Los datos provienen de múltiples estudios que involucraron a más de 1,100 pacientes en más de 60 centros a nivel mundial.
Los hallazgos clave incluyen resultados de dos estudios neoadyuvantes (UNICORN y NEST) con más de 80 pacientes, mostrando tasas prometedoras de respuesta completa patológica: 93% en tumores dMMR/MSI-H y 29% en tumores pMMR/MSS. En el tratamiento de primera línea, la combinación con FOLFOX-Bevacizumab alcanzó un 71% de tasa de respuesta global en 14 pacientes.
Un estudio global de Fase 2 con 234 pacientes demostró un 19% de tasa de respuesta global y un 55% de tasa de control de enfermedad en mCRC MSS refractario, con un 70% de las respuestas ongoing en el momento de la recolección de datos. La terapia mostró un particular potencial en el tratamiento de tumores CRC microsatélites estables (MSS), que representan el 85-95% de los casos de CRC y típicamente no responden a la inmunoterapia.
Agenus (NASDAQ: AGEN)는 ASCO GI에서 botensilimab (BOT) 및 balstilimab (BAL) 조합 요법에 대한 새로운 데이터를 발표하며 대장암 (CRC) 치료에서 중요한 가능성을 보여주었습니다. 이 데이터는 전 세계 60개 이상의 센터에서 1,100명 이상의 환자를 포함한 여러 연구에서 얻은 것입니다.
주요 발견에는 80명 이상의 환자를 대상으로 한 두 개의 보조 요법 연구 (UNICORN 및 NEST)에서의 결과가 포함되며, dMMR/MSI-H 종양에서 93%, pMMR/MSS 종양에서 29%의 유망한 병리학적 완전 반응률을 보여줍니다. 1차 치료에서, FOLFOX-Bevacizumab과의 조합이 14명의 환자에서 71%의 전체 반응률을 달성했습니다.
234명의 환자를 대상으로 한 글로벌 2상 연구에서는 refractory MSS mCRC에서 19%의 전체 반응률과 55%의 질병 조절률을 입증하였으며, 데이터 커트오프 시점에서 응답 중 70%가 지속 중이었습니다. 이 요법은 85-95%의 CRC 사례를 차지하고 일반적으로 면역 치료에 반응하지 않는 마이크로새틀라이트 안정성 (MSS) CRC 종양 치료에 특히 유망한 것으로 나타났습니다.
Agenus (NASDAQ: AGEN) a présenté de nouvelles données sur la thérapie combinée avec botensilimab (BOT) et balstilimab (BAL) lors de l'ASCO GI, montrant un potentiel significatif dans le traitement du cancer colorectal (CRC). Les données proviennent de plusieurs études impliquant plus de 1 100 patients dans plus de 60 centres à travers le monde.
Les résultats clés incluent ceux de deux études néoadjuvantes (UNICORN et NEST) avec plus de 80 patients, montrant des taux prometteurs de réponse complète pathologique : 93 % dans les tumeurs dMMR/MSI-H et 29 % dans les tumeurs pMMR/MSS. En traitement de première ligne, la combinaison avec FOLFOX-Bevacizumab a atteint un taux de réponse global de 71 % chez 14 patients.
Une étude mondiale de Phase 2 avec 234 patients a démontré un taux de réponse global de 19 % et un taux de contrôle de la maladie de 55 % chez les mCRC MSS réfractaires, avec 70 % des réponses en cours au moment de la collecte des données. La thérapie a montré un potentiel particulier dans le traitement des tumeurs CRC stables par microsatellite (MSS), qui représentent 85 à 95 % des cas de CRC et qui ne répondent généralement pas à l'immunothérapie.
Agenus (NASDAQ: AGEN) präsentierte neue Daten zur Kombinationstherapie mit botensilimab (BOT) und balstilimab (BAL) auf dem ASCO GI, die ein signifikantes Potenzial in der Behandlung von kolorektalem Krebs (CRC) zeigen. Die Daten stammen aus mehreren Studien, an denen über 1.100 Patienten in mehr als 60 Zentren weltweit beteiligt waren.
Zu den wichtigsten Ergebnissen gehören Ergebnisse aus zwei neoadjuvanten Studien (UNICORN und NEST) mit über 80 Patienten, die vielversprechende Raten vollständiger pathologischer Antworten zeigen: 93% bei dMMR/MSI-H Tumoren und 29% bei pMMR/MSS Tumoren. Bei der Erstlinientherapie erzielte die Kombination mit FOLFOX-Bevacizumab eine Gesamtansprechrate von 71% bei 14 Patienten.
Eine globale Phase-2-Studie mit 234 Patienten zeigte eine Gesamtansprechrate von 19% und eine Krankheitskontrollrate von 55% bei refraktärem MSS mCRC, wobei 70% der Antworten zum Zeitpunkt des Daten-Cut-offs weiterhin anhielten. Die Therapie zeigte insbesondere bei der Behandlung von mikrosatellitenstabilen (MSS) CRC Tumoren, die 85-95% der CRC-Fälle ausmachen und typischerweise nicht auf Immuntherapie ansprechen, vielversprechende Ergebnisse.
- High response rates in neoadjuvant setting: 93% pCR in dMMR/MSI-H tumors
- 71% overall response rate in first-line treatment with FOLFOX-Bevacizumab
- 19% ORR and 55% disease control rate in refractory MSS mCRC
- 70% of responses ongoing at data cut-off, showing durability
- Favorable safety profile with severe immune-mediated adverse events
- Phase 3 trials still pending
- Strategic transactions required to launch registrational trials
- Therapy not yet approved in any jurisdiction
Insights
The clinical trial results presented by Agenus at ASCO GI represent a potential breakthrough in colorectal cancer treatment, particularly for the 85-95% of patients with microsatellite stable (MSS) tumors who currently have treatment options. The BOT/BAL combination therapy has shown remarkable efficacy across multiple treatment settings:
In the neoadjuvant setting (treatment before surgery), two independent studies (UNICORN and NEST) involving over 80 patients demonstrated impressive results:
- A 29% complete elimination of cancer cells (pathological complete response) in MSS tumors
- A 93% complete response rate in MSI-H tumors
- Excellent safety profile with only 5% treatment-related serious adverse events
For context, achieving any response in MSS colorectal cancer with immunotherapy has been historically challenging, making these results particularly significant. The data suggests potential for reducing reliance on chemotherapy and surgery in some patients - a paradigm shift in treatment approach.
In the advanced disease setting, the Phase 2 trial involving 234 patients showed:
- 19% objective response rate in heavily pre-treated patients
- 70% of responses were ongoing at data cutoff
- Superior efficacy compared to standard treatments (regorafenib or trifluridine/tipiracil)
From a commercial perspective, these results position Agenus's therapy as a potential new standard of care across multiple treatment lines. The company's strategy to pursue registrational trials following strategic transactions (partnerships, licensing, or joint ventures) could accelerate market access while sharing development costs.
The clinical data presented significantly strengthens Agenus's position in the immuno-oncology market, particularly in colorectal cancer treatment. With a current market cap of
Market Opportunity Analysis:
- Colorectal cancer treatment market is projected to reach
$16.5 billion by 2026 - MSS CRC represents 85-95% of cases, a largely untapped market for immunotherapy
- Multiple treatment settings (neoadjuvant, first-line, refractory) expand the potential revenue streams
The company's strategy to pursue strategic transactions for registrational trials is financially prudent, considering:
- Reduced capital requirements through partnership funding
- Potential upfront payments and milestone revenues
- Shared development risks
- Accelerated path to market
The robust data across multiple trials and treatment settings strengthens Agenus's negotiating position for potential partnerships or licensing deals. The demonstrated efficacy in MSS CRC, particularly in the neoadjuvant setting where it could reduce reliance on surgery and chemotherapy, represents a significant value proposition for potential partners and investors.
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Results from two independent neoadjuvant studies in the
U.S. andEurope , enrolling more than 80 patients, underscore BOT/BAL’s potential to enable chemo-free and non-operative approaches in colorectal cancer (CRC). - New randomized Phase 2 results in over 230 patients with refractory MSS mCRC, consistent with Phase 1 data, demonstrate durable responses and a favorable safety profile.
- Strong activity demonstrated with BOT/BAL in first-line and rechallenged MSS mCRC in combination with chemotherapy and targeted therapies shows synergy and tolerability in a large patient population.
"Data presented at ASCO GI highlight botensilimab and balstilimab’s potential to redefine colorectal cancer treatment, delivering remarkable outcomes in neoadjuvant MSS CRC," said Dr. Steven O’Day, Chief Medical Officer of Agenus. "These findings set the stage for pivotal studies intended to create a new standard of care for colon and rectal cancer patients by reducing reliance on chemotherapy, radiation, and surgery, while improving survival.”
Key Data Highlights
Neoadjuvant CRC: A Potential Path to Chemo-Free Treatment
Data presented from two independent studies, UNICORN and NEST, collectively include more than 80 patients treated with BOT/BAL:
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UNICORN: Phase 2 Trial of Pre-Operative BOT/BAL Combination Treatment in Resectable Colon Cancer (Abstract 158):
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This multicenter Phase 2 study enrolled 56 patients across 10 centers in
Italy andFrance . - Pathological complete responses (pCR) and pathological major responses (pMR) were observed in both the pMMR/MSS and dMMR/MSI-H patient populations.
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BOT/BAL achieved a
93% pCR rate and100% pMR in dMMR/MSI-H tumors and29% pCR rate and36% pMR rate in pMMR/MSS tumors, highlighting the opportunity for a non-operative, organ sparing, approach in this disease setting. -
Serious adverse events (AEs) occurred in 9 pts (
16% ) and were treatment-related in 3 pts (5% ). Only 1 of 56 surgeries were delayed due to an AE.
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This multicenter Phase 2 study enrolled 56 patients across 10 centers in
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NEST: Phase 2 Trial of Neoadjuvant Combination Treatment of BOT/BAL in Patients with Resectable Colon Cancer (Abstract 207):
- This trial has currently enrolled 24 patients.
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After median follow-up of 18 months (NEST-1 arm) and 9 months (NEST-2 arm), all patients (
100% ) remained ctDNA negative and no clinical recurrences were observed. The pMR improved in NEST-2 to47% (7/15) in MSS tumors when the median time to surgery was extended. - The combination was well tolerated with no grade 4 events and no unresolved immune-mediated adverse events (imAEs). No delays in surgery occurred due to imAEs.
Dr. Filippo Pietrantonio, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori Milan comments on the UNICORN study stating, "These results further validate the transformative potential of botensilimab and balstilimab in colorectal cancer. The remarkable pathological response rates observed in both pMMR and dMMR tumors highlight the unique strength of this combination in addressing a critical unmet need and pave the way for non-operative management strategies.”
First-Line and FOLFOX Rechallenged MSS CRC: Powerful Combination with Standard Therapies
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Phase 1/2 Trial of BOT/BAL With FOLFOX-Bevacizumab in MSS mCRC (Abstract 180):
- Preliminary findings showed activity of combination independent of liver metastases.
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In the initial 14 patients, 12 which were previously treated with FOLFOX, a
71% overall response rate (ORR) was achieved. In the 9/14 patients with liver metastases, a67% ORR was achieved. - The combination was well-tolerated with limited severe imAEs, supporting the opportunity for higher doses of BOT.
Refractory MSS CRC: Consistent Results Across Phase 1 and 2 Studies
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Global Randomized Phase 2 Study of BOT/BAL in MSS mCRC NLM (Abstract 23):
- This is a global Phase 2 trial (NCT05608044) of BOT/BAL versus standard-of-care treatments of regorafenib or trifluridine/tipiracil in patients with refractory metastatic colorectal cancer that had spread to either peritoneum, lymph nodes, lungs, bone or brain. 234 patients were enrolled across 40 centers worldwide.
- These results reinforce the activity and safety seen in the Phase 1 study and confirm the contribution of BAL to BOT.
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BOT75/BAL achieved a
19% ORR and55% disease control rate (DCR) in this refractory population. Standard of care had no responses. -
70% of responses were ongoing at the time of data cut-off, demonstrating durability as DOR continues to mature. - BOT/BAL showed a superior benefit-risk profile at 75 mg compared to BOT/BAL 150mg and has been selected for Phase 3 trials.
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No new safety signals were observed, and no treatment related deaths occurred. The most common imAEs at BOT 75mg + BAL included diarrhea/colitis (
35% ) and hypothyroidism (13% ).
“The Phase 2 results highlight the unique and consistent activity of the botensilimab and balstilimab combination, demonstrating a compelling objective response rate in microsatellite stable metastatic colorectal cancer, a disease where responses to immunotherapy have historically been absent,” said Dr. Marwan Fakih, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center. “These findings underscore the potential of botensilimab and balstilimab combination treatment in addressing this critical unmet need, paving the way for further investigation.”
Gastric Cancer
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Phase 2 BOT/BAL/AgenT-797 in Combination with Ramucirumab and Paclitaxel in Patients with Previously Treated, Unresectable or Metastatic Gastroesophageal Cancers (Abstract TPS515):
- The Phase 2 trial (NCT06251973) is investigating a novel combination approach, which leverages cellular therapy and immune modulation to address the unmet needs in gastroesophageal cancers. Gastroesophageal cancers continue to be a growing global burden responsible for nearly 1.3 million global deaths annually2.
- The novel approach demonstrated early signals of activity and tolerability in the second-line treatment setting, with additional efficacy data anticipated in 2H 2025.
Future Development Plans
Agenus has developed registrational enabling trials in MSS CRC across neoadjuvant, first-line, and late-line settings. These trials will launch upon completion of strategic transactions. Upon the options being considered are, partnerships, licensing, or joint ventures. These initiatives aim to accelerate global access to BOT/BOL to deliver transformative patient outcomes and drive substantial value for stakeholders.
Botensilimab, balstilimab, and agenT-797 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide.
For additional data and publications, visit agenusbio.com/publications.
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
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.
About Balstilimab (BAL)
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in >900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types.
About AgenT-797
AgenT-797 is an allogeneic invariant natural killer T (iNKT) cell therapy, leveraging a unique innate immune cell type that serves as a master regulator of both innate and adaptive immunity. iNKTs combine the cytotoxic capabilities of natural killer (NK) cells with the adaptive memory of T cells, enabling them to elicit a broad range of immune responses in a pathogen-agnostic manner.
AgenT-797 is a scalable, “off-the-shelf” cell therapy product, manufactured by MiNK Therapeutics in
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.
1 Ros J et al. Front Oncol 2023;13:1112276; 2. André T et al. Am Soc Clin Oncol Educ Book 2022;42:1-9;
2 eClinicalMedicine, 2022
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FAQ
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