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

Servier

Status and phase: Completed; Phase 2; Phase 1

Conditions: IDH1-mutant Cholangiocarcinoma

Treatments: Drug: Nivolumab; Drug: Ipilimumab; Drug: Ivosidenib; Drug: Recommended Combination Dose (RCD) of ivosidenib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05921760

CL1-95031-006

Details and patient eligibility

About

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.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

7 participants in 3 patient groups

Safety Lead-In Phase - ivosidenib

Experimental group

Description:

First phase of the study.

Treatment:

Drug: Ivosidenib

Drug: Ipilimumab

Drug: Nivolumab

Experimental Phase - Cohort 1

Experimental group

Description:

Second phase of the study. Cohort 1 will include the anti-PD1/L1-naïve subpopulation.

Treatment:

Drug: Recommended Combination Dose (RCD) of ivosidenib

Drug: Ipilimumab

Drug: Nivolumab

Experimental Phase - Cohort 2

Experimental group

Description:

Second phase of the study. Cohort 2 will include the anti-PD1/L1 previously treated subpopulation.

Treatment:

Drug: Recommended Combination Dose (RCD) of ivosidenib

Drug: Ipilimumab

Drug: Nivolumab