BAL/BOT/agenT-797 in pMMR CRC With Liver Metastases

NCT07550088 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: SC-CRC-IST-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn whether the combination of balstilimab, botensilimab, and agenT-797 is safe and effective in treating adults with previously treated metastatic colorectal cancer that is microsatellite stable (pMMR) and has spread to the liver. The main questions it aims to answer are:

• What proportion of participants experience tumor shrinkage (objective response rate) based on imaging assessments?
• What side effects occur with this combination treatment, including immune-related and cytokine-related reactions? All participants in this study will receive the combination treatment. There is no comparison group. Participants will:
• Receive balstilimab, botensilimab, and agenT-797 in repeating 42-day treatment cycles
• Undergo imaging scans (such as CT or MRI) to assess tumor response
• Have blood samples collected to monitor safety and evaluate biomarkers
• Provide tumor tissue samples for research
• Be monitored for side effects throughout the study
• Participate in follow-up visits to assess survival after treatment completion

Conditions

Colorectal Cancer Metastatic

Keywords

Metastatic Colorectal Cancer; pMMR Colorectal Cancer; Liver Metastases; Immunotherapy; Checkpoint Inhibitor; Anti-PD-1; Anti-CTLA-4; iNKT Cell Therapy; Balstilimab; Botensilimab; agenT-797; MSS Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR, defined as the proportion of participants whose best overall response (BOR) is either Complete Response (CR) or Partial Response (PR) per RECIST v1.1.

  From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).

Secondary Outcomes (7)

• Overall response rate in liver metastasis (ORLM)

  From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).

• Progression free survival (PFS) at 6 months (PFS6)

  At 6 months from enrollment

• Progression Free Survival (PFS) at 12 months (PFS12)

  At 12 months from enrollment

• Overall Survival (OS)

  From enrollment until death from any cause

• Time to Tumor Response (TTR)

  From enrollment until first documented complete (CR) or partial response (CR) per RECIST v1.1 (up to approximately 12 months).

Other Outcomes (2)

• Changes in circulating tumor DNA (ctDNA) from baseline during study treatment in responders and non-responders, per RECIST1.1.

  From baseline through post-baseline ctDNA assessments up to End of Treatment (approximately 12 months).

• Immunophenotyping and Immune Profiling of Peripheral Blood and Tumor Microenvironment (TME)

  From baseline through longitudinal immune profiling assessments during study treatment and at End of Treatment (up to approximately 12 months).

Study Arms (1)

Treatment arm

EXPERIMENTAL

balstilimab (BAL) + botensilimab (BOT) + agenT-797

Drug: Balstilimab (BAL); Drug: Botensilimab (BOT); Drug: agenT-797

Interventions

Balstilimab (BAL) DRUG

Administered at a fixed dose of 240mg intravenously (IV) on Days 1, 15, 29 of each 42-day cycle, for up to 9 cycles.

Also known as: AGEN2034

Treatment arm

Botensilimab (BOT) DRUG

Administered at a fixed dose of 75mg IV on Day 1 of Cycles 1 through 4. In the event of protocol-defined toxicity, the dose may be reduced to 50mg IV per protocol defined criteria.

Also known as: AGEN1181

Treatment arm

agenT-797 DRUG

Administered at a dose of 1.4 x 107 cells/kg IV on Day 1 of Cycle 1 and Day 15 of Cycle 2.

Also known as: allo-INKTs

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years of age with histologically confirmed metastatic colorectal cancer with liver metastases, including evidence of active liver disease if previously treated locally
• At least one measurable lesion per RECIST v1.1, with ≥1 target lesion in the liver
• Tumor confirmed as microsatellite stable (MSS)/proficient mismatch repair (pMMR)
• Received ≥1 prior line of systemic therapy including fluorouracil, oxaliplatin, and irinotecan (not necessarily in combination), and prior EGFR inhibitor or bevacizumab if eligible, unless contraindicated
• ECOG performance status 0-1 and life expectancy ≥12 weeks
• Adequate organ and marrow function:
• ANC ≥1.5 × 10⁹/L
• Platelets ≥100 × 10⁹/L
• Hemoglobin ≥8 g/dL
• AST/ALT ≤2.5 × ULN
• Total bilirubin ≤1.5 × ULN
• Creatinine clearance ≥30 mL/min
• Albumin ≥3 g/dL
• PT/PTT ≤1.5 × ULN
• Willing and able to provide written informed consent

You may not qualify if:

• Tumor is dMMR/MSI-high
• Prior treatment with PD-1, PD-L1, CTLA-4 inhibitors, or other immunotherapy agents
• Evidence of bowel obstruction, impending obstruction, or recent obstruction (within 3 months)
• Refractory ascites requiring frequent paracentesis or recent escalation of diuretics
• Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke, unstable angina, NYHA class ≥III heart failure, uncontrolled arrhythmias) or QTc \>480 ms
• Active or untreated brain metastases or leptomeningeal disease
• Concurrent malignancy requiring treatment or active within 2 years (with protocol-specified exceptions)
• Receipt of prior anti-cancer therapy within protocol-defined washout periods, including:
• Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
• Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
• Small molecules/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half-lives of investigational drug.
• Known hypersensitivity to study drugs or excipients
• History of or active interstitial lung disease or pneumonitis requiring systemic steroids
• Prior allogeneic transplant (organ, stem cell, or bone marrow)
• Active or recent autoimmune disease requiring systemic treatment

Sponsors & Collaborators

• Darren Sigal, MD: lead
• Scripps Health: collaborator

Study Sites (1)

Scripps Clinic Torrey Pines

La Jolla, California, 92037, United States

Location

Related Publications (10)

• Parekh VV, Lalani S, Kim S, Halder R, Azuma M, Yagita H, Kumar V, Wu L, Kaer LV. PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J Immunol. 2009 Mar 1;182(5):2816-26. doi: 10.4049/jimmunol.0803648.

  PMID: 19234176 BACKGROUND

• Andre T, Elez E, Lenz HJ, Jensen LH, Touchefeu Y, Van Cutsem E, Garcia-Carbonero R, Tougeron D, Mendez GA, Schenker M, de la Fouchardiere C, Limon ML, Yoshino T, Li J, Manzano Mozo JL, Dahan L, Tortora G, Chalabi M, Goekkurt E, Braghiroli MI, Joshi R, Cil T, Aubin F, Cela E, Chen T, Lei M, Jin L, Blum SI, Lonardi S. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial. Lancet. 2025 Feb 1;405(10476):383-395. doi: 10.1016/S0140-6736(24)02848-4. Epub 2025 Jan 25.

  PMID: 39874977 BACKGROUND

• Liu Y, Wang G, Chai D, Dang Y, Zheng J, Li H. iNKT: A new avenue for CAR-based cancer immunotherapy. Transl Oncol. 2022 Mar;17:101342. doi: 10.1016/j.tranon.2022.101342. Epub 2022 Jan 18.

  PMID: 35063813 BACKGROUND

• Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol. 2023 Feb 10;14:1133308. doi: 10.3389/fimmu.2023.1133308. eCollection 2023.

  PMID: 36845131 BACKGROUND

• Bullock AJ, Schlechter BL, Fakih MG, Tsimberidou AM, Grossman JE, Gordon MS, Wilky BA, Pimentel A, Mahadevan D, Balmanoukian AS, Sanborn RE, Schwartz GK, Abou-Alfa GK, Segal NH, Bockorny B, Moser JC, Sharma S, Patel JM, Wu W, Chand D, Rosenthal K, Mednick G, Delepine C, Curiel TJ, Stebbing J, Lenz HJ, O'Day SJ, El-Khoueiry AB. Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial. Nat Med. 2024 Sep;30(9):2558-2567. doi: 10.1038/s41591-024-03083-7. Epub 2024 Jun 13.

  PMID: 38871975 BACKGROUND

• Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, Sobrero A, Boucher E, Peeters M, Tran B, Lenz HJ, Zaniboni A, Hochster H, Cleary JM, Prenen H, Benedetti F, Mizuguchi H, Makris L, Ito M, Ohtsu A; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015 May 14;372(20):1909-19. doi: 10.1056/NEJMoa1414325.

  PMID: 25970050 BACKGROUND

• Overman MJ, Lonardi S, Leone F, et al. Nivolumab in patients with DNA mismatch repair deficient/microsatellite instability high metastatic colorectal cancer: Update from CheckMate 142. Journal of Clinical Oncology. 2017;35(4_suppl):519-519. doi:10.1200/JCO.2017.35.4_suppl.519

  BACKGROUND

• Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8.

  PMID: 28596308 BACKGROUND

• Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.

  PMID: 26457759 BACKGROUND

• Siegel RL, Kratzer TB, Wagle NS, Sung H, Jemal A. Cancer statistics, 2026. CA Cancer J Clin. 2026 Jan-Feb;76(1):e70043. doi: 10.3322/caac.70043.

  PMID: 41528114 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

balstilimab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, GI Oncology Division of Hematology/Oncology

Model Details: All participants in this study will receive the combination treatment. There is no comparison group.

Study Record Dates

• First Submitted: April 15, 2026
• First Posted: April 24, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)