PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS 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 bevacizumab and mFOLFOX6 as first line therapy in patients with metastatic microsatellite stable (MSS) colorectal cancer. The study was to have assessed primarily, the safety and tolerability and then the efficacy of PDR001 in combination with bevacizumab and mFOLFOX6. Particular attention would have been paid to the level of activity of study drug combinations in CMS4 patients (retrospective analysis). The study was terminated early due to company decision.

Official Title
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ElevatION: CRC-101: A Phase Ib Study of PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: PDR001
* Drug: bevacizumab
* Drug: mFOLFOX6


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Patients with metastatic MSS colorectal adenocarcinoma.Note: MSI status will be performed locally by an immunohistochemistry (IHC) or PCR based test for eligibility. Patients must provide a newly obtained or an archival tumor sample corresponding to CRC diagnosis (primary tumor) with sufficient tissue quality (qualified) for analysis (mandatory) Patients must provide a newly obtained tumor tissue sample from a metastatic site (mandatory) Patients who are naïve to systemic treatment in metastatic setting. Patients with previous neoadjuvant or adjuvant chemotherapy (that may have included oxaliplatin or investigational VEGF inhibitors) are eligible if the treatment was completed > 12 months before inclusion. Patients with the presence of at least one lesion with measurable disease as per RECIST 1.1 guidelines. Lesions in previously irradiated areas should not be considered measurable unless they have clearly progressed since the radiotherapy. 9. Patients have 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 received any systemic treatment for metastatic disease. Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CTLA-4 antibodies, other checkpoint inhibitors Patients who had received radiation within 14 days prior to the first dose of study drug Other protocol-defined inclusion/exclusion criteria may apply

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 Ib study, safety run-in (N= 6 pts) followed with an expansion (N= 86 pts). One single arm: PDR001 in combination with bevacizumab and mFOLFOX6
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDR001<br> | Drug: PDR001<br>* 400 mg every 4 weeks<br>Drug: bevacizumab<br>* 5 mg/kg every 2 weeks<br>Drug: mFOLFOX6<br>* Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2)<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) |  | 12 months | 
| Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 | RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1 | 19 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) per central assessment using RECIST v1.1 |  | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit | 
| Overall survival (OS) |  | Every 3 months after last visit up to 1 year after last patient last visit | 
| Progression free survival |  | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit | 
| Duration of response (DOR) |  | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit | 
| Disease control rate (DCR) |  | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit | 
| Time to response (TTR) |  | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit | 
| Ctrough |  | Through end of treatment completion, an average of 14 months | 
| Cmax |  | Through end of treatment completion, an average of 14 months | 
| Area under the curve (AUC) |  | Through end of treatment completion, an average of 14 months | 
| Antidrug antibodies (ADA) |  | Through end of treatment completion, an average of 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MMS, CRC, PDR001, immunotherapy, bevacizumab, mFOLFOX6, CMS4, ElevatION;CRC-101