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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: spartalizumab (PDR001); Drug: regorafenib

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Novartis Investigative Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Novartis Investigative Site
• Israel
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key inclusion criteria:

1. Patients with metastatic colorectal adenocarcinoma.
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
3. Patients must provide a newly obtained tumor tissue sample from a metastatic site
4. Patients with the presence of at least one lesion with measurable disease as per RECIST
5. 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).
6. Patient has 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 had chemotherapy, radiation, or biological cancer therapy within 14 days prior to the first dose of study treatment
4. Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti- CTLA-4 antibodies, other checkpoint inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Novartis results database
• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 9, 2017
• Primary Completion (ACTUAL): May 7, 2019
• Study Completion (ACTUAL): May 7, 2019

Study Registration Dates

• First Submitted: March 10, 2017
• First Submitted That Met QC Criteria: March 10, 2017
• First Posted (ACTUAL): March 16, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: immunotherapy; PDR001; CRC; regorafenib; MMS; MCC; CMS4; ElevatION:CRC-102
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CPDR001I2102; 2017-000466-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No