Pan-tumor Neoadjuvant Basket Study of Immune Check-point Inhibition and Novel Immuno-oncology Combinations

Sponsor
The Netherlands Cancer Institute
Study ID
NCT06279130
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

  • Resectable MMR-deficient Solid Tumors
  • Resectable MMR-proficient Solid Tumors

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • botensilimab — DRUG
    Anti cytotoxic T-lymphocyte associated protein-4 (anti-CTLA4)
  • balstilimab — DRUG
    Anti programmed cell death protein-1 (anti-PD1)
  • FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) — DRUG
    5-Fluorouracil (2400mg/m2), leucovorin (200mg/m2), oxaliplatin (85mg/m2), docetaxel (50mg/m2).

Study Details

In this study, the efficacy of botensilimab and balstilimab in mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors will be assessed.

Key Dates

Start date
Jan 29, 2024
Status verified
Mar 2026
Primary completion
Jan 29, 2029
Completion
Jan 29, 2034

Study Design

Enrollment
133 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 2: pMMR Safety run-in 1 - closed (accrual reached)
    5 Patients will be included and will be treated with 2 cycles of neoadjuvant immunotherapy consisting of 450mg balstilimab and 25mg botensilimab in Cycle 1 and 450mg balstilimab in Cycle 2 followed by surgery Accrual was reached in June 2024, cohort is closed.
  • Experimental: Cohort 4: pMMR Safety run-in 2 - closed (accrual reached)
    5 Patients will be included and will be treated with 2 cycles of neoadjuvant immunotherapy consisting of 450mg balstilimab and 50mg botensilimab in Cycle 1 and 450mg balstilimab in Cycle 2 followed by surgery Accrual was reached in August 2024, cohort is closed.
  • Experimental: Cohort 1: dMMR Safety run-in 1 - closed (accrual reached)
    5 Patients will be included and will be treated with 2 cycles of neoadjuvant immunotherapy consisting of 450mg balstilimab and 25mg botensilimab in Cycle 1 and 450mg balstilimab in Cycle 2 followed by surgery Accrual was reached in June 2025, cohort is closed.
  • Experimental: Cohort 3: dMMR Safety run-in 2 - closed (accrual reached)
    5 Patients will be included and will be treated with 2 cycles of neoadjuvant immunotherapy consisting of 450mg balstilimab and 50mg botensilimab in Cycle 1 and 450mg balstilimab in Cycle 2 followed by surgery Acrrual was reached in August 2024, cohort is closed.
  • Experimental: Cohort 6: dMMR Colorectal basket - closed (accrual reached)
    Patients with resectable colon and rectal cancer will be treated with the regimen assesses as safe and feasible in the dMMR safety run-in. Treatment will be administered at day 1 and day 22 followed by surgery 8 weeks after registration. Accrual will be temporarily halted after accrual of the first 8 patients. If \>2 major pathological responses are observed accrual will continue to a total of 18 patients. Accrual was reached in July 2025, cohort is closed.
  • Experimental: Cohort 5: dMMR Upper gastro-intestinal cancer basket
    Patients with resectable oesophageal (adenocarcinoma), gastro-oesophageal junction, gastric and small bowel cancer will be treated with the regimen assessed as safe and feasible in the dMMR safety run-in. Treatment will be administered at day 1 and day 22 followed by surgery 8 weeks after registration. Accrual will be temporarily halted after accrual of the first 8 patients. If \>2 major pathological responses are observed accrual will continue to a total of 18 patients.
  • Experimental: Cohort 7: dMMR "other cancers" basket
    Patients with resectable solid tumors of various origins such as but not limited to breast-, prostate-, bladder cancer, Head\&Neck SCC, oesophageal SCC and sarcoma will be treated with the regimen assessed as safe and feasible in the dMMR safety run-in. Treatment will be administered at day 1 and day 22 followed by surgery 8 weeks after registration. Accrual will be temporarily halted after accrual of the first 8 patients. If \>2 major pathological responses are observed accrual will continue to a total of 18 patients.
  • Experimental: Cohort 8: pMMR TNBC cohort
    Patients with resectable Triple Negative Breast Cancer will be treated with the regimen assessed as safe and feasible in the pMMR safety run-in. Treatment will be administered at day 1 and day 22 followed by surgery 8 weeks after registration. Accrual will be temporarily halted after accrual of the first 8 patients. If \>2 major pathological responses are observed accrual will continue to a total of 18 patients.
  • Experimental: Cohort 9: pMMR "other cancers" - cohort closed
    Patients with resectable pMMR tumors of various origins will be treated with the regimen assessed as safe and feasible in the pMMR safety run-in. Treatment will be administered at day 1 and day 22 followed by surgery 8 weeks after registration. Accrual will be temporarily halted after accrual of the first 8 patients. If \>2 major pathological responses are observed accrual will continue to a total of 18 patients. Accrual was halted after 8 patients in July 2025, not more then 2 major pathological responses were observed, cohort remains closed.
  • Experimental: Cohort 10: pMMR GEA basket
    Patients with pMMR gastro-, esophageal or GE-junction tumors will receive study treatment that consists of cycle 1) botensilimab 50mg plus balstilimab 240mg 2) FLOT + bal 240mg 3) FLOT plus bot 50mg/bal 240mg 4-5) FLOT + bal 240mg. Surgery will take place a maximum of 6 weeks after start last treatment cycle. Patients will receive 8mg dexamethasone as premedication for docetaxel on the first day of infusion, and no additional doses of dexamethasone are allowed in the following days as an anti-emetic. Post-surgery, patients may receive 4 additional cycles of FLOT according to the standard of care. Evaluation will be performed after the first 3 patients are treated; if the proposed treatment is deemed feasible and all patients received the intended chemotherapy regimen, accrual may continue with the next 3 patients. If the first three patients undergo surgery according to plan without delays that are considered immune-related, accrual may continue beyond six patients (max 21).
  • Experimental: Cohort 11: dMMR Rectal Organ Preservation basket
    Patients with stage I-III dMMR rectal adenocarcinoma who prefer organ preservation are eligible. The study treatment will consist of 1 cycle of combination therapy on day 1: botensilimab 50mg plus balstilimab 450mg, followed by 2 cycles of balstilimab 450mg monotherapy on day 22 and day 43. If at the 1st response evaluation at 10 weeks a limited response, no response or progressive disease is observed, treatment according to standard of care, which may consist of direct surgery or additional neoadjuvant therapy may be considered after discussion in the MDT and with the study team.

Primary Outcome Measure

Major pathological response rate [ Time Frame: Week 8 ]

Central Contacts