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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT03176264
Collaborator
(none)
1
1
1
4.2
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Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
1 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention 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 mFOLFOX6Phase 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)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 25, 2017
Actual Primary Completion Date :
Jan 30, 2018
Actual Study Completion Date :
Jan 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: PDR001

Drug: PDR001
400 mg every 4 weeks

Drug: bevacizumab
5 mg/kg every 2 weeks

Drug: mFOLFOX6
Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2)

Outcome Measures

Primary Outcome Measures

  1. Incidence of Dose-limiting toxicity (DLT) [12 months]

  2. Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 [19 months]

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

Secondary Outcome Measures

  1. 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]

  2. Overall survival (OS) [Every 3 months after last visit up to 1 year after last patient last visit]

  3. Progression free survival [Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit]

  4. Duration of response (DOR) [Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit]

  5. Disease control rate (DCR) [Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit]

  6. Time to response (TTR) [Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit]

  7. Ctrough [Through end of treatment completion, an average of 14 months]

  8. Cmax [Through end of treatment completion, an average of 14 months]

  9. Area under the curve (AUC) [Through end of treatment completion, an average of 14 months]

  10. Antidrug antibodies (ADA) [Through end of treatment completion, an average of 14 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key inclusion criteria:
  1. Patients with metastatic MSS colorectal adenocarcinoma.Note: MSI status will be performed locally by an immunohistochemistry (IHC) or PCR based test for eligibility.

  2. 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)

  3. Patients must provide a newly obtained tumor tissue sample from a metastatic site (mandatory)

  4. 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.

  5. 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.

  6. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Key exclusion criteria:
  1. Patients with MSI-H colorectal adenocarcinoma as defined per local assessment using standard of care testing

  2. Patients with metastatic disease amenable to be resected with potentially curative surgery

  3. Patients who have received any systemic treatment for metastatic disease.

  4. Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CTLA-4 antibodies, other checkpoint inhibitors

  5. Patients who had received radiation within 14 days prior to the first dose of study drug

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

Site City State Country Postal Code
1 Novartis Investigative Site Sutton Surrey United Kingdom SM2 5PT

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Principal Investigator: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03176264
Other Study ID Numbers:
  • CPDR001I2101
  • 2017-000520-96
First Posted:
Jun 5, 2017
Last Update Posted:
Oct 12, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 12, 2021