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Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma

Servier Protocol Code: CL1-95031-006 Sponsor: Servier Bio-Innovation LLC Clinicaltrials.gov Identifier: NCT05921760 EU Trial (CTIS) Number: 2023-503236-41-00

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How to participate to the study?
If you think you are eligible for this study (see
eligibility criteria
below), you can identify the location closest to you and contact them directly. If you don’t find a location close to you, please contact Institut de Recherches Internationales Servier (I.R.I.S.)
Name: Institut de Recherches Internationales Servier, Département des études cliniques
Phone number: +33 1 55 72 60 00
The study has 5 locations

Study description

This is a Phase 1/2 study evaluating the safety, tolerability, and activity of ivosidenib in combination with immunotherapy in participants with nonresectable or metastatic cholangiocarcinoma. The study includes two phases: the safety lead-in phase to determine the recommended combination dose (RCD) of ivosidenib in combination with immunotherapy and the dose expansion phase to assess the efficacy of ivosidenib in combination with immunotherapy. Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met.
Official title: A Phase 1/2, Safety Lead-in and Dose Expansion, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Nivolumab and Ipilimumab in Previously Treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Conditions
IDH1-mutant Cholangiocarcinoma
Interventions / Treatments
  • Ivosidenib
  • Recommended Combination Dose (RCD) of ivosidenib
  • Nivolumab
  • Ipilimumab
Other study id numbers
  • CL1-95031-006

Eligibility Criteria

Eligible age for the study

18 years and older (Adult, Older Adult)

Sexes

Male/Female

Accepts Healthy Volunteers

No

  • * Male of female participant age ≥ 18 years old
  • * Have documented IDH1 gene-mutated disease based on local testing procedure (R132C/L/G/H/S mutations variants tested)
  • * Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
  • * Has a histopathological diagnosis consistent with nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies
  • * Participants must have at least one measurable lesion as defined by RECIST Version 1.1. Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or if within the field but has shown ≥ 20% growth in size post-treatment assessment.

  • * Received prior treatment with an IDH inhibitor or prior treatment with an immune checkpoint inhibitor other than anti-PD1/L1
  • * Have active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment
  • * Participants who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 1 non-hematologic toxicity, according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, prior to the first IMP administration. Residual Grade ≤ 2 toxicity from chemotherapy (e.g., alopecia, neuropathy) may be allowed.
  • * Have known symptomatic brain metastases requiring steroids. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and have radiographically stable disease for at least 3 months prior to study entry. Note: Up to 10 mg per day of prednisone equivalent will be allowed.

How is the study designed?

Allocation
Non-randomized
Interventional study model
Parallel
Participant Group / Arm
Experimental: Safety Lead-In Phase - ivosidenib
First phase of the study.
Intervention / Treatment
Drug: Ivosidenib
ivosidenib taken once daily
Drug: Nivolumab
Nivolumab taken by intravenous infusion
Drug: Ipilimumab
Ipilimumab taken by intravenous infusion
Participant Group / Arm
Experimental: Experimental Phase - Cohort 1
Second phase of the study. Cohort 1 will include the anti-PD1/L1-naïve subpopulation.
Intervention / Treatment
Drug: Recommended Combination Dose (RCD) of ivosidenib
The RCD of ivosidenib taken once daily
Drug: Nivolumab
Nivolumab taken by intravenous infusion
Drug: Ipilimumab
Ipilimumab taken by intravenous infusion
Participant Group / Arm
Experimental: Experimental Phase - Cohort 2
Second phase of the study. Cohort 2 will include the anti-PD1/L1 previously treated subpopulation.
Intervention / Treatment
Drug: Recommended Combination Dose (RCD) of ivosidenib
The RCD of ivosidenib taken once daily
Drug: Nivolumab
Nivolumab taken by intravenous infusion
Drug: Ipilimumab
Ipilimumab taken by intravenous infusion