Pepinemab in Combination With Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Summary

Objectives

The purpose of the study is to evaluate the safety and tolerability of pepinemab in
combination with pembrolizumab as first-line treatment and determine a recommended Phase
2 dose (RP2D) in patients with recurrent or metastatic head and neck squamous cell
carcinoma (R/M HNSCC). The study will consist of a safety run in phase and a dose
expansion phase.

The primary objective of the Safety Run-in phase of the study is to evaluate the safety
and tolerability of pepinemab in combination with pembrolizumab as first-line treatment
and determine a recommended Phase 2 dose (RP2D) for the dose-expansion phase enrolling
subjects in patients with recurrent or metastatic head and neck squamous cell carcinoma
(R/M HNSCC).

The primary objective of the Dose Expansion phase of the study is to evaluate objective
response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of the
combination of pepinemab/pembrolizumab in immunotherapy naïve patients with R/M HNSCC.

The secondary objectives of the study are to evaluate progression-free survival (PFS) by
RECIST 1.1 of the combination of pepinemab/pembrolizumab in immunotherapy naïve patients
with R/M HNSCC, to evaluate the overall survival (OS), and to evaluate the duration of
response (DOR).

The exploratory objectives of the study are to evaluate PFS, ORR, and DOR via the iRECIST
criteria, to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and
immunogenicity of the combination, to investigate the relationship between treatment with
pepinemab and pembrolizumab and certain biomarkers and the genomic signatures of baseline
or archival tumor samples.

The Safety Run-in phase will enroll a minimum of 3 subject and a maximum of 18 subjects
who will be treated with intravenous pepinemab IV (starting at 20 mg/kg, with potential
dose modifications to 15 mg/kg or 10 mg/kg) and pembrolizumab at 200 mg IV, Q3W. The Dose
Expansion phase of the study will enroll a maximum of approximately 62 subjects who will
be treated with intravenous pepinemab administered IV at the RP2D, plus pembrolizumab 200
mg IV, Q3W.

Subjects will undergo evaluation for extent of disease (EOD) at baseline, week 9, every 6
weeks through year 1, and every 9 weeks thereafter. Subjects who discontinue study
treatment will continue to be followed for survival every 12 weeks after safety follow-up
(for up to approximately 2 years).