Daiichi Sankyo has entered into a clinical trial collaboration agreement with Merck KGaA, Darmstadt, Germany and Pfizer, Inc. to evaluate the combination of [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), in combination with the checkpoint inhibitor avelumab and/or an investigational Merck KGaA, Darmstadt, Germany DNA damage response (DDR) inhibitor, in patients with HER2 expressing or mutated solid tumors.  

A separate research collaboration to conduct preclinical studies evaluating [fam-] trastuzumab deruxtecan in combination with avelumab, the DDR inhibitor and other investigational compounds in Merck KGaA, Darmstadt, Germany’s and Pfizer’s pipelines is also underway.

“The collaboration is another milestone in our development strategy to maximize the potential of [fam-] trastuzumab deruxtecan for various HER2 expressing and mutated cancers in combination with immunotherapy and other agents with novel mechanisms of action,” said Tom Held, vice president, Head, Antibody Drug Conjugate Task Force, Oncology Research and Development, Daiichi Sankyo. “We look forward to working with Merck KGaA, Darmstadt, Germany and Pfizer to determine an appropriate combination strategy to help further improve outcomes for patients. In particular, we are enthusiastic about better understanding the potential of combining [fam-] trastuzumab deruxtecan with DNA damage response agents.” 

Under the terms of the agreement, Daiichi Sankyo will conduct a three-part phase 1b multicenter, open-label study to determine the safety and efficacy of [fam-] trastuzumab deruxtecan in combination with avelumab and/or a DDR inhibitor.  

The first part of the study (Part A) will include a dose-escalation and dose-expansion phase to evaluate the maximum tolerated dose, safety and efficacy of [fam-] trastuzumab deruxtecan in combination with avelumab. Patients with HER2 expressing cancer refractory to standard treatment will be enrolled into the dose-escalation phase of Part A of the study. Four cohorts of patients will be enrolled into the dose-expansion phase.

The second part of the study (Part B) will include a dose-escalation and dose-expansion phase to evaluate the maximum tolerated dose, safety and efficacy of [fam-] trastuzumab deruxtecan in combination with the DDR inhibitor in patients with HER2 expressing or mutated advanced/metastatic solid tumors.

The third part of the study (Part C) will evaluate the triple combination of [fam-] trastuzumab deruxtecan, avelumab and the DDR inhibitor in patients with HER2 expressing cancer once the recommended expansion doses are known from Parts A and B.

The primary endpoints of each part of the study are maximum tolerated dose, recommended expansion dose and objective response rate. Secondary endpoints include duration of response, disease control rate, progression-free survival, overall survival, time to response and key safety endpoints. The study is expected to enroll approximately 200 patients in the U.S., Europe and Asia.