Pfizer, Merck KGaA Collaboration Accelerates PD-L1 Inhibitor Development

Mikael Dolsten, MD, PhD

Pfizer and Merck KGaA have agreed to collaborate on the development of the PD-L1 inhibitor MSB0010718C as a potential treatment for multiple types of cancer, the companies announced in joint statements. Under the agreement, Merck KGaA will receive an upfront payment of $850 million and will be eligible to receive regulatory and commercial milestone payments of up to approximately $2 billion.

The companies plan to launch 20 clinical trials focused on immunotherapeutic approaches in oncology, with 6 of these trials geared toward regulatory approval. Both companies will jointly fund all development and commercialization costs for MSB0010718C. Additionally, Pfizer and Merck KGaA will work together to develop Pfizer’s anti-PD-1 antibody in phase I trials. Clinical trials under the new agreement are expected to commence in 2015.

“Up to 20 high priority immuno-oncology clinical development programs are expected to commence in 2015, including pivotal registration studies,” Belén Garijo, president and chief executive officer of Merck’s biopharmaceutical division Merck Serono, said in a statement. “On top of that, the global alliance will enable Merck to gain an early entry into the US oncology market as well as to strengthen our existing oncology business in several other important global markets.”

MSB0010718C is a fully human IgG1 monoclonal antibody that binds to the PD-L1. The drug is currently being assessed in two early phase clinical trials for patients with solid tumors.

In a phase I trial presented at the 2014 ASCO Annual Meeting, 27 patients with refractory malignancies were treated with MSB0010718C at 1, 3, 10, and 20 mg/kg twice weekly. Eleven patients on the study had received prior treatment with an immunotherapy. This analysis assessed target receptor occupancy and pharmacokinetics (PK) of the drug.

At the 3- and 10-mg/kg doses, the drug was found to inhibit 93.8% and 93.2% of the PD-L1 receptor on peripheral leukocytes. Additionally, a linear PK profile was found, with a maximum concentration of the drug achieved at 1.5 - 2 hours following infusion. At the 20-mg/kg dose, a dose-limiting immune-related adverse was noted.

“Early results for Merck KGaA’s PD-L1 in patient trials are impressive and consistent with the results seen with the class of PD-1 and PD-L1 antibodies,” Mikael Dolsten, MD, PhD, president of Pfizer Worldwide Research and Development and executive vice president, Pfizer, said of the early phase results. “This promising foundation of research will form the basis of multiple registration trials.”

A large phase I study is currently exploring the tolerability and clinical activity of MSB0010718C in patients with metastatic or locally advanced solid tumors. This study plans to enroll 825 patients across 7 treatment cohorts. To date, the study has recruited 550 patients. In a September 2014 analyst call, Merck KGaA noted that treatment with MSB0010718C elicited complete and partial responses in patients with non-small cell lung cancer and ovarian cancer in the study. Additional data are expected in 2015.

“Immuno-oncology is a top priority for Pfizer. Combining this promising anti-PD-L1 antibody with Pfizer’s extensive portfolio of small molecules and antibodies, provides an opportunity to potentially broaden the use of immunotherapy for patients with cancer and rapidly expand our oncology business,” Albert Bourla, group president Vaccines, Oncology and Consumer Healthcare Businesses, Pfizer, said in a statement. "In addition, this alliance enables us to significantly accelerate the timeframe of our development programs and move into the first wave of potential immuno-oncology based treatment regimens.”

In July 2014, the first patient began treatment with MSB0010718C in a large phase II study investigating the safety and efficacy of the drug in patients with Merkel cell carcinoma, a type of rare skin cancer. The primary outcome measure of this study is best overall response, with progression-free survival and duration of response as secondary outcomes measures. The study plans to enroll 84 patients.