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

Purpose

This is a phase Ib study of PDR001 in combination with regorafenib in adult patients with previously treated metastatic microsatellite stable (MSS) colorectal cancer. The study will assess primarily the safety and tolerability and then the efficacy of PDR001 in combination with regorafenib. Particular attention will be paid to the level of activity of study drug combinations in CMS4 patients (retrospective analysis).

Condition	Intervention	Phase
Metastatic Colorectal Cancer	Drug: PDR001 Drug: regorafenib	Phase 1


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Intervention Model Description: Phase 1b study, dose escalation (N=~12) followed with an expansion (N=~60). One single arm: PDR001 in combination with regorafenib Masking: No masking Primary Purpose: Treatment
Official Title:	Phase Ib Study of PDR001 in Combination With Regorafenib in Adult Patients With Previously Treated Metastatic Microsatellite Stable (MSS) Colorectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Colorectal Cancer

Drug Information available for: Regorafenib

U.S. FDA Resources

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:

Incidence of Dose-limiting toxicity (DLT) [ Time Frame: 12 months ]
Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 [ Time Frame: 23 months ]
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 [ Time Frame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit ]
Overall survival (OS) [ Time Frame: Every 3 months after last visit up to 1 year after last patient first treatment ]
Progression free survival (PFS) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient last visit ]
Duration of response (DOR) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient last visit ]
Time to response (TTR) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient last visit ]
Cmax [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 21, Cycle 4 Day 1, Cycle 4 Day 21, Cycle 6 Day 1, Cycle 6 Day 21, Cycle 8 Day 21, Cycle 12 Day 1 and then every 6 cycles until end of treatment ]
Area under the curve (AUC) [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 21, Cycle 4 Day 1, Cycle 4 Day 21, Cycle 6 Day 1, Cycle 6 Day 21, Cycle 8 Day 21, Cycle 12 Day 1 and then every 6 cycles until end of treatment ]
Ctrough [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 21, Cycle 4 Day 1, Cycle 4 Day 21, Cycle 6 Day 1, Cycle 6 Day 21, Cycle 8 Day 21, Cycle 12 Day 1 and then every 6 cycles until end of treatment ]
Antidrug antibodies (ADA) [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, Cycle 10 Day 1, Cycle 12 Day 1, and then every 6 cycles until end of treatment ]


Estimated Enrollment:	72
Actual Study Start Date:	June 9, 2017
Estimated Study Completion Date:	November 11, 2019
Estimated Primary Completion Date:	November 11, 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PDR001	Drug: PDR001 400 mg every 4 weeks Drug: regorafenib either 160 or 120 or 80 mg once daily first 21 days of each 28-day cycle (=4 weeks) Other Name: Stivarga®

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03081494

Contacts


Contact: Novartis Pharmaceuticals	1-888-669-6682	novartis.email@novartis.com
Contact: Novartis Pharmaceuticals	+41613241111	novartis.email@novartis.com

Locations


Australia, New South Wales
Novartis Investigative Site	Recruiting
St. Leonards, New South Wales, Australia, 2065
Australia, Western Australia
Novartis Investigative Site	Recruiting
Murdoch, Western Australia, Australia, 6150
Canada, Quebec
Novartis Investigative Site	Recruiting
Montreal, Quebec, Canada, H3T 1E2
Spain
Novartis Investigative Site	Recruiting
Barcelona, Catalunya, Spain, 08035

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT03081494 History of Changes
Other Study ID Numbers:	CPDR001I2102 2017-000466-30 ( EudraCT Number )
Study First Received:	March 10, 2017
Last Updated:	July 11, 2017
Individual Participant Data (IPD) Sharing Statement:
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 ( Novartis Pharmaceuticals ):


PDR001 immunotherapy regorafenib CRC	MMS CMS4 ElevatION:CRC-102

Additional relevant MeSH terms:


Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms	Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases

ClinicalTrials.gov processed this record on July 17, 2017