Clinical trial NCT03176264: PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer
Official title: ElevatION: CRC-101: A Phase Ib Study of PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Keywords: PDR001
immunotherapy
bevacizumab
mFOLFOX6
CRC
MMS
CMS4
ElevatION;CRC-101
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-06-05
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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.


Eligibility 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/exclusion criteria may apply

Primary outcomes:
measure: Incidence of Dose-limiting toxicity (DLT)
timeFrame: 12 months
measure: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1
timeFrame: 19 months
Secondary outcomes:
measure: Overall response rate (ORR) per central assessment using RECIST v1.1
timeFrame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
measure: Overall survival (OS)
timeFrame: Every 3 months after last visit up to 1 year after last patient last visit
measure: Progression free survival
timeFrame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
measure: Duration of response (DOR)
timeFrame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
measure: Disease control rate (DCR)
timeFrame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
measure: Time to response (TTR)
timeFrame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
measure: Ctrough
timeFrame: Through end of treatment completion, an average of 14 months
measure: Cmax
timeFrame: Through end of treatment completion, an average of 14 months
measure: Area under the curve (AUC)
timeFrame: Through end of treatment completion, an average of 14 months
measure: Antidrug antibodies (ADA)
timeFrame: Through end of treatment completion, an average of 14 months
Other outcomes:
Locations:
city: Sutton
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: PRINCIPAL_INVESTIGATOR
References: