NCT05268510

Chemotherapy and Pembrolizumab, Followed by Pembrolizumab and Olaparib As Firstline Therapy in Her-2 Negative Gastric/GEJ Adenocarcinoma

Phase IIA Trial of Short-term Chemotherapy and Pembrolizumab, Followed by Pembrolizumab and Olaparib As Firstline Therapy in Her-2 Negative Gastric/gastroesophageal-junction (GEJ) Adenocarcinoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, single arm, prospective, open-label phase II trial investigating the clinical activity of a first-line therapy consisting of induction chemotherapy plus pembrolizumab (12 weeks of mod. FOLFOX-6 plus pembrolizumab or 12 weeks of CAPOX plus pembrolizumab) followed by pembrolizumab plus olaparib.

Detailed description

Her-2 negative patients suffering from metastatic or unresectable gastric/GEJ adenocarcinoma will be included in the study. Eligible subjects will receive 2 six-week (q42d) cycles of mod. FOLFOX-6 plus pembrolizumab. Alternatively, subjects may receive 2 six-week (q42d) cycles of CAPOX plus pembrolizumab. The decision for either mod. FOLFOX-6 or CAPOX is made at the sole discretion of the investigator taking into account the best interest of the patient. Following the chemotherapy induction phase, the subjects are scheduled to receive pembrolizumab plus olaparib until tumor progression or occurrence of limiting toxicity for a maximum of 16 cycles (q42d, total 18 cycles, approx. 2 years). The primary objective of this phase II study is to assess the overall survival at 1 year. Secondary objectives are the assessment of the objective response rate, the best overall response, progression-free survival, overall survival and treatment feasibility rate along with safety and toxicity of the treatment. The exploratory objective is to assess whether clinical efficacy correlates with molecularly-defined subgroups (PD-L1 expression, HR alterations, MSI subtypes, and others). The study will be accompanied by an explorative translational research analysis of blood and tumor samples. The compositional changes of leukocyte states and their gene expression changes under combination immunotherapy will be analyzed using single cell RNA sequencing. Using factor analysis methods, we will analyze the environmental cues shaping leukocyte states and compare these features in responders and non-responders to therapy and correlate these with overall and progression-free survival. In addition, centralized PD-L1 expression and molecular sequencing of tumor tissue will be performed with a focus on alterations of HRD pathway.

Conditions

• Esophagogastric Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	400 mg Pembrolizumab day 1 Q6W (max. 18 cycles)
DRUG	Olaparib	300 mg Olaparib bid. cont. day 1 to 42 (max. 16 cycles)
DRUG	mFOLFOX-6	Oxaliplatin 85 mg/m² 2h day 1, 15, 29 plus Leucovorin 400 mg/m² 2h day 1, 15, 29 plus 5-FU 400 mg/m² bolus, followed by 2.400 mg/m² 46h day 1, 15, 29; Q6W, 2 cycles
DRUG	CapOX	Oxaliplatin 130 mg/m² 2h day 1,22 plus Capecitabine 1.000 mg/m² bid. day 1-14, 22-35; Q6W, 2 cycles

Timeline

• Start date: 2022-09-15
• Primary completion: 2024-08-27
• Completion: 2025-01-09
• First posted: 2022-03-07
• Last updated: 2025-02-20

Locations

1 site across 1 country: Germany