Metastatic Colorectal Cancer
Conditions
Keywords
PDR001, MCC, immunotherapy, regorafenib, CRC, MMS, CMS4, ElevatION:CRC-102
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.
Interventions
DRUGspartalizumab (PDR001)
100 mg lyophilisate in vial received 400 mg every 4 weeks
DRUGregorafenib
120 mg once daily first 21 days of each 28-day cycle (=4 weeks)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1b study, dose escalation (N=\ 12). One single arm: PDR001 in combination with regorafenib
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Canada, Israel, Italy, Netherlands, Singapore, South Korea, Spain
Outcome results
None listed