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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03081494

Collaborator

(none)

Enrollment

Locations

Arm

22.9

Actual Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: spartalizumab (PDR001) Drug: regorafenib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Phase 1b study, dose escalation (N=~12). One single arm: PDR001 in combination with regorafenibPhase 1b study, dose escalation (N=~12). One single arm: PDR001 in combination with regorafenib

Masking:

None (Open Label)

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

Actual Study Start Date :

Jun 9, 2017

Actual Primary Completion Date :

May 7, 2019

Actual Study Completion Date :

May 7, 2019

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

Incidence of Dose-limiting toxicity (DLT) [8 Weeks]
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.

Secondary Outcome Measures

Incidence of adverse events (AEs) and serious adverse events (SAEs) [Up to 150 days after last administration of PDR001]
Incidence of all treatment-emergent adverse events (including clinically significant changes in laboratory values, vital signs and ECG), as assessed by CTCAE v4.03.
Severity of AEs and SAEs [Up to 150 days after last administration of PDR001]
Severity including dose interruptions and reductions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	St Leonards	New South Wales	Australia	2065
2	Novartis Investigative Site	Murdoch	Western Australia	Australia	6150
3	Novartis Investigative Site	Montreal	Quebec	Canada	H3T 1E2
4	Novartis Investigative Site	Tel Aviv		Israel	6423906
5	Novartis Investigative Site	Milano	MI	Italy	20162
6	Novartis Investigative Site	Rozzano	MI	Italy	20089
7	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
8	Novartis Investigative Site	Leiden		Netherlands	2333 ZA
9	Novartis Investigative Site	Singapore		Singapore	169610
10	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
11	Novartis Investigative Site	Madrid		Spain	28041