Metastatic Colorectal Cancer
Conditions
Keywords
PDR001, immunotherapy, bevacizumab, mFOLFOX6, CRC, MMS, CMS4, ElevatION;CRC-101
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.
Interventions
DRUGPDR001
400 mg every 4 weeks
DRUGbevacizumab
5 mg/kg every 2 weeks
DRUGmFOLFOX6
Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 mFOLFOX6
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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. 9\. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-limiting toxicity (DLT) | 12 months | — |
| 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
| Measure | Time frame |
|---|---|
| Cmax | Through end of treatment completion, an average of 14 months |
| 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 |
| Overall survival (OS) | Every 3 months after last visit up to 1 year after last patient last visit |
| Progression free survival | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit |
| Area under the curve (AUC) | Through end of treatment completion, an average of 14 months |
| Disease control rate (DCR) | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit |
| Time to response (TTR) | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit |
| Ctrough | Through end of treatment completion, an average of 14 months |
| Duration of response (DOR) | Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit |
| Antidrug antibodies (ADA) | Through end of treatment completion, an average of 14 months |
Countries
United Kingdom
Outcome results
None listed