Abstract 3469
Background
Monoclonal antibodies against checkpoint inhibitors (CHKPNT) such as pembrolizumab showed clinical benefit in patients with microsatellite instability (MSI) in mCRC but not in MSS patients. Cancer vaccines with ADC could be a complementary therapeutic approach to CHKPNT. We previously conducted a negative randomized phase II trial in mCRC patients refractory to standard therapy, with ADC compared to the best supportive (Eur J Cancer 64:167-74, 2016). A phase I-II multicentric trial with avelumab (anti-PD-L1) plus ADC vaccine in pre-treated MSS mCRC patients began in April 2018 (NCT03152565).
Trial design
The study is designed to evaluate the safety, tolerability, pharmacodynamics and anti-tumour effects of the combination in pre-treated MSS mCRC patients. In the phase I, patients are assigned using a standard 3x3 de-escalation criteria (level -1 if dose limiting toxicity (DLT) with avelumab 3 mg/kg every 2 weeks) to received avelumab at a dose of 10 mg/kg every 2 weeks combined to ADC vaccine at days 1, 14, 28, 42 and 56, and thereafter every 6 months until disease progression (maximum of 6 additional doses) or unacceptable toxicity. Biopsies to prepare tumour lysate will be obtained from primary tumour or metastatic disease. The primary objective is to determine the maximum tolerated dose (MTD) and the efficacy of the combination. To detect at least a 20% difference in PFS at 6 months (from 20% to 40%), 33 patients are needed (80% power, alpha equals 5%, two sided). An interim analysis (Simon’s two stage) when the first 18 patients are accrued is planned. Secondary objective includes pharmacodynamics (a) NanoString 360 gene immune-signature from archival biopsy, at study entry and at 2 months therapy (b) cytokine and chemokine determination (at study entry and at 2 months therapy) and (c) Autologous tumour mixed leucocyte reaction to test the polarisation of the immune response against the combination (at study entry and at 2 months therapy).
Clinical trial identification
NCTO3152565.
Legal entity responsible for the study
Grupo Español Multidisciplinar de Melanoma.
Funding
Merck.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.