Phase Ib Study of PDR001 in Combination With Regorafenib in Adult Patients With Previously Treated Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This was a phase Ib study of PDR001 in combination with regorafenib in adult patients with previously treated metastatic microsatellite stable (MSS) colorectal cancer. The study assessed primarily the safety and tolerability of PDR001 in combination with regorafenib.

Official Title
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Phase Ib Study of PDR001 in Combination With Regorafenib in Adult Patients With Previously Treated Metastatic Microsatellite Stable (MSS) Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: spartalizumab (PDR001)
* Drug: regorafenib


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Patients with metastatic colorectal adenocarcinoma. Patients must provide a newly obtained or an archival tumor sample corresponding to CRC diagnosis (primary tumor) with sufficient tissue quality (qualified) for analysis Patients must provide a newly obtained tumor tissue sample from a metastatic site Patients with the presence of at least one lesion with measurable disease as per RECIST Patients previously treated with two prior regimen as per standard of care and have experienced disease progression (including -VEGF and EGFR targeted therapies (if KRAS wild). Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Key exclusion criteria: Patients with MSI-H colorectal adenocarcinoma as defined per local assessment using standard of care testing Patients with metastatic disease amenable to be resected with potentially curative surgery Patients who have had chemotherapy, radiation, or biological cancer therapy within 14 days prior to the first dose of study treatment Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti- CTLA-4 antibodies, other checkpoint inhibitors

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
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1b study, dose escalation (N= 12). One single arm: PDR001 in combination with regorafenib
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: spartalizumab (PDR001) + regorafenib<br>Subjects with metastatic MSS CRC received a combination of spartalizumab and regorafenib. | Drug: spartalizumab (PDR001)<br>* 100 mg lyophilisate in vial received 400 mg every 4 weeks<br>* Other names: PDR001;Drug: regorafenib<br>* 120 mg once daily first 21 days of each 28-day cycle (=4 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose-limiting toxicity (DLT) | A dose-limiting toxicity (DLT) was defined as (1) an adverse event or abnormal laboratory value (assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications) that occurred within the first 8 weeks (56 days) of treatment with PDR001 in combination with regorafenib during dose escalation part and (2) met any of the pre-defined criteria. | 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | Incidence of all treatment-emergent adverse events (including clinically significant changes in laboratory values, vital signs and ECG), as assessed by CTCAE v4.03. | Up to 150 days after last administration of PDR001 | 
| Severity of AEs and SAEs | Severity including dose interruptions and reductions. | Up to 150 days after last administration of PDR001 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDR001, MCC, immunotherapy, regorafenib, CRC, MMS, CMS4, ElevatION:CRC-102