IPH5401 (Anti-C5aR) in Combination With Durvalumab in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, antitumor activity of IPH5401 (anti C5aR) in combination with Durvalumab (MEDI4736) in Adult Subjects with selected advanced solid tumors.

Official Title
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A Phase I Study of the Anti-C5aR, IPH5401, in Combination With the Anti-PD-L1, Durvalumab, in Patients With Selected Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: IPH5401 and Durvalumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced and/or metastatic histologically solid tumors with evidence of active disease, who have been treated with a minimum of one line of systemic therapy in the metastatic setting, and in expansion part, no more than two prior systemic therapies. At least 18 years of age. ECOG performance status of ≤1. Adequate organ function Exclusion Criteria: For patients with Non Small Cell Lung Cancer (NSCLC): a. Known actionable mutation or rearrangement (including but not limited to the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangements, ROS-1 alterations or BRAF mutations) For patient with Hepatocellular carcinoma (HCC): Hepatic encephalopathy in the past 12 months. Ascites that requires repeated paracentesis in the past 2 months. Main portal vein thrombosis. Active or prior history of gastrointestinal bleeding in the past 12 months. Prior hepatic transplantation. Patients with known spinal cord compression. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>IPH5401 at different doses and schedule + Durvalumab | Biological: IPH5401 and Durvalumab<br>* IPH5401 and durvalumab<br>|
| Experimental: Cohort expansion NSCLC anti-PD-(L)1 pretreated<br>IPH5401 at recommended dose and schedule + Durvalumab in NSCLC anti-PD-(L)1 pretreated patients | Biological: IPH5401 and Durvalumab<br>* IPH5401 and durvalumab<br>|
| Experimental: Cohort expansion HCC anti-PD-(L)1 naive<br>IPH5401 at recommended dose and schedule + Durvalumab in HCC anti-PD-(L)1 naive patients | Biological: IPH5401 and Durvalumab<br>* IPH5401 and durvalumab<br>|
| Experimental: Cohort expansion HCC anti-PD-(L)1 pretreated<br>IPH5401 at recommended dose and schedule + Durvalumab in HCC anti-PD-(L)1 pretreated patients | Biological: IPH5401 and Durvalumab<br>* IPH5401 and durvalumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Drug Limited Toxicities (DLTs) | To assess the occurrence of Drug Limited Toxicities (DLTs) | From Time of First dose assessed up to 6 weeks | 
| Adverse events (AEs) | To evaluate the safety profile | From screening visit up to 30 days after the last dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Rate of patients in complete or partial response according to RECIST 1.1 | up to 12 months | 
| Duration of Response | duration between the complete or partial response and the first documented progression | 2 years and 9 months | 
| Progression Free Survival | time between the start of treatment and the first documented progression or death | 2 years and 9 months |