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Colorectal Cancer MetastaticPhase 2NCT07550088

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

A Phase 2 study testing Balstilimab (BAL), Botensilimab (BOT) and agenT-797 in people with Colorectal Cancer Metastatic, run by Darren Sigal, MD at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer Metastatic
What is being tested?
Balstilimab (BAL), Botensilimab (BOT) and agenT-797
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
10 Jun 2026to Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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) per a FDA-approved assay (Caris MI Cancer Seek®, FoundationOne® CDx, or Tempus xT CDx).
  • 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:
Show all 17Show fewer
  • ANC ≥1.5 × 10⁹/L
  • Platelets ≥100 × 10⁹/L
  • Hemoglobin ≥ 9 g/dL
  • AST/ALT ≤2.5 × ULN
  • Total bilirubin ≤1.5 × ULN
  • Creatinine clearance ≥ 40 mL/min, as measured or calculated per local institutional standards.
  • Albumin ≥3 g/dL
  • PT/PTT ≤1.5 × ULN
  • Willing and able to provide written informed consent
  • Negative pregnancy test for women of childbearing potential
  • Agreement to use effective contraception during study participation

Who cannot join

  • 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
Show all 23Show fewer
  • 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
  • Requirement for systemic corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive therapy within defined windows
  • Active infection, including HIV, HTLV, HBV, HCV, or other infections requiring systemic therapy
  • Recent SARS-CoV-2 infection within protocol-defined timeframe
  • Uncontrolled hypertension, significant proteinuria (UPCR ≥1 g/g), or other clinically significant uncontrolled medical conditions
  • Non-healing wounds, active bleeding, or uncontrolled thyroid dysfunction
  • Psychiatric or substance use disorders that may interfere with study participation
  • Receipt of live or attenuated vaccines within 30 days prior to treatment and while participating in the study
  • Pregnant or breastfeeding women, or those planning pregnancy during the study

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • Scripps Clinic Torrey Pines

    La Jolla, California, 92037

    Darren Sigal Principal Investigator, MD, 858-554-8788, CRSLeadership@scrippshealth.org

    Recruiting

Other trials in United States

About this study

Official title: A Single-Arm, Phase II Study Evaluating Combination Balstilimab Plus Botensilimab With AgenT-797 in Previously Treated Patients With pMMR Metastatic CRC With Liver Metastases

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:

Read more
  • 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
Read the detailed description

This is a Phase II, single-arm, investigator-sponsored clinical trial evaluating the safety and efficacy of the combination of balstilimab (anti-PD-1), botensilimab (Fc-enhanced anti-CTLA-4), and agenT-797 (allogeneic invariant natural killer T [iNKT] cell therapy) in patients with previously treated microsatellite stable (pMMR) metastatic colorectal cancer with liver metastases.

Patients with pMMR/MSS metastatic colorectal cancer derive limited benefit from currently available immunotherapy approaches. The liver tumor microenvironment is associated with immune tolerance and resistance to checkpoint blockade. This study is designed to evaluate whether combining dual checkpoint inhibition with cellular therapy can enhance anti-tumor immune responses and improve clinical outcomes in this population.

The primary objective of the study is to evaluate the objective response rate (ORR) as assessed by RECIST v1.1. Secondary objectives include evaluation of safety and tolerability, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory objectives include assessment of biomarkers such as circulating tumor DNA (ctDNA), tumor markers, and immune-related correlates.

Participants will receive combination treatment in 42-day cycles for up to nine cycles or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Balstilimab and botensilimab will be administered in combination with agenT-797 according to the study protocol.

Tumor assessments will be performed using CT or MRI at regular intervals to evaluate response per RECIST v1.1. Safety will be monitored throughout the study through assessment of adverse events, laboratory evaluations, and clinical examinations, with particular attention to immune-mediated and cytokine-related toxicities.

Blood samples will be collected for safety monitoring and exploratory biomarker analyses, including ctDNA and immune profiling. Archival tumor tissue will be collected when available, and on-study biopsies may be obtained to support correlative research.

Following completion of study treatment, participants will undergo a safety follow-up period and will be followed for survival at regular intervals.

Being tested
Balstilimab (BAL), Botensilimab (BOT), agenT-797
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
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Balstilimab (BAL)Drug

    Also called AGEN2034

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

  • Botensilimab (BOT)Drug

    Also called AGEN1181

    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.

  • agenT-797Drug

    Also called allo-INKTs

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

Study groups in NCT07550088
Study groupRoleWhat they receive
Treatment armExperimentalbalstilimab (BAL) + botensilimab (BOT) + agenT-797
Receives: Drug: Balstilimab (BAL); Drug: Botensilimab (BOT); Drug: agenT-797

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (7)

  1. Overall response rate in liver metastasis (ORLM)

    ORLM, defined as the proportion of participants whose best overall response (BOR) in liver target lesions is Complete Response (CR-Liver) or Partial Response (PR-Liver) per RECIST v1.1.

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

  2. Progression free survival (PFS) at 6 months (PFS6)

    Proportion of participants alive and progression-free at 6 months

    Measured: At 6 months from enrollment

  3. Progression Free Survival (PFS) at 12 months (PFS12)

    Proportion of participants alive and progression-free at 12 months

    Measured: At 12 months from enrollment

  4. Overall Survival (OS)

    Defined as the time interval from date of enrollment to death from any cause.

    Measured: From enrollment until death from any cause

  5. Time to Tumor Response (TTR)

    Defined as the time interval from date of enrollment to date of the first documented CR or PR per RECIST v1.1.

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

  6. Duration of Response (DOR)

    Defined as the time interval from date of first documented CR or PR to the earliest date of documented tumor progression or death from any cause, whichever occurs first.

    Measured: From date of first documented CR or PR per RECIST v1.1 to date of disease progression or death from any cause, whichever occurs first (up to approximately 12 months).

  7. Biochemical response (CEA and/or CA 19-9)

    Defined as ≥ 50% reduction from baseline in serum CEA and/or CA 19-9 levels.

    Measured: From enrollment until completion of biomarker assessments (up to approximately 12 months).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2026
  2. Study start10 Jun 2026
  3. Primary completionSep 2028 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
All participants in this study will receive the combination treatment. There is no comparison group.
Masking
None (open label)
Enrolment
17 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07550088
Sponsor's protocol ID
SC-CRC-IST-01
Status last verified
Apr 2026
First submitted
15 Apr 2026
Last updated
10 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 19234176

  • 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.

    PubMed 39874977

  • 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.

    PubMed 35063813

  • 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.

    PubMed 36845131

  • 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.

    PubMed 38871975

  • 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.

    PubMed 25970050

  • 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

  • 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.

    PubMed 28596308

  • 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.

    PubMed 26457759

  • 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.

    PubMed 41528114

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Balstilimab (BAL), Botensilimab (BOT) and agenT-797 in people with Colorectal Cancer Metastatic, run by Darren Sigal, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07550088, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.

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