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PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer

Primary Purpose

Metastatic Colorectal Cancer

Status

Terminated

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

PDR001

bevacizumab

mFOLFOX6

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring PDR001, immunotherapy, bevacizumab, mFOLFOX6, CRC, MMS, CMS4, ElevatION;CRC-101

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PDR001

Arm Description

Outcomes

Primary Outcome Measures

Incidence of Dose-limiting toxicity (DLT)

Overall Response Rate (ORR) per investigator assessment using RECIST v1.1

RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1

Secondary Outcome Measures

Overall response rate (ORR) per central assessment using RECIST v1.1

Overall survival (OS)

Progression free survival

Duration of response (DOR)

Disease control rate (DCR)

Time to response (TTR)

Ctrough

Cmax

Area under the curve (AUC)

Antidrug antibodies (ADA)

Full Information

NCT ID

NCT03176264

First Posted

May 25, 2017

Last Updated

October 7, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03176264

Brief Title

PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Terminated

Why Stopped

The study was terminated early due to company decision.

Study Start Date

September 25, 2017 (Actual)

Primary Completion Date

January 30, 2018 (Actual)

Study Completion Date

January 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

Keywords

PDR001, immunotherapy, bevacizumab, mFOLFOX6, CRC, MMS, CMS4, ElevatION;CRC-101

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PDR001

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

PDR001

Intervention Description

400 mg every 4 weeks

Intervention Type

Drug

Intervention Name(s)

bevacizumab

Intervention Description

5 mg/kg every 2 weeks

Intervention Type

Drug

Intervention Name(s)

mFOLFOX6

Intervention Description

Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2)

Primary Outcome Measure Information:

Title

Incidence of Dose-limiting toxicity (DLT)

Time Frame

12 months

Title

Overall Response Rate (ORR) per investigator assessment using RECIST v1.1

Description

RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1

Time Frame

19 months

Secondary Outcome Measure Information:

Title

Overall response rate (ORR) per central assessment using RECIST v1.1

Time Frame

Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit

Title

Overall survival (OS)

Time Frame

Every 3 months after last visit up to 1 year after last patient last visit

Title

Progression free survival

Time Frame

Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit

Title

Duration of response (DOR)

Time Frame

Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit

Title

Disease control rate (DCR)

Time Frame

Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit

Title

Time to response (TTR)

Time Frame

Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit

Title

Ctrough

Time Frame

Through end of treatment completion, an average of 14 months

Title

Cmax

Time Frame

Through end of treatment completion, an average of 14 months

Title

Area under the curve (AUC)

Time Frame

Through end of treatment completion, an average of 14 months

Title

Antidrug antibodies (ADA)

Time Frame

Through end of treatment completion, an average of 14 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Principal Investigator

Facility Information:

Facility Name

Novartis Investigative Site

City

Sutton

State/Province

Surrey

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17317

Description

Novartis results database

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=651

Description

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer

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