Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer

A Phase 1b, Open-Label, Single-Arm Dose-Expansion Study of IK-175, an Oral Aryl Hydrocarbon Receptor Inhibitor, in Combination With Nivolumab in Patients With Primary PD-1 Inhibitor Resistant Metastatic or Locally Incurable, Recurrent HNSCC

This is a phase 1b study in adult patients diagnosed with resistant or recurrent head and neck squamous cell carcinoma (HNSCC) designed to assess the safety and tolerability of IK-175 in combination with nivolumab. Disease response, pharmacokinetics (PK), pharmacodynamics, and response biomarkers will also be assessed.

This is an open-label, multicenter, phase 1b dose-expansion study to evaluate the safety, tolerability, preliminary antitumor activity, PK, and pharmacodynamics of 2 dose levels of IK-175, administered PO in combination with nivolumab, in patients with primary PD-1-resistant metastatic or locally incurable, recurrent HNSCC for which standard therapy is no longer effective or is intolerable.

Key Inclusion Criteria:

• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Subject has a histologically confirmed metastatic or locally incurable, recurrent HNSCC that has progressed within 12 weeks of initiation of PD-1 inhibitor agent, whether it was administered alone or in combination with chemotherapy.
• Tumors must express PD-L1 with a minimum CPS ≥ 1.
• Subjects can be enrolled regardless of their tumor's expression of human papillomavirus (HPV).
• Subjects are required to have received prior treatment with a platinum-based chemotherapy in the recurrent or metastatic disease setting, unless medically contraindicated.
• Subject has at least 1 measurable lesion per RECIST v1.1.

Key Exclusion Criteria:

• Subject has untreated or symptomatic central nervous system (CNS) tumors or brain metastases.
• Subject must have recovered to ≤ Grade 1 from clinically significant AEs related to prior therapy (eg, myelosuppression or renal or hepatic dysfunction.)
• Subject has received prior treatment with an AHR inhibitor.
• Subject has a medical condition that limits oral administration or impairment of gastrointestinal function that is expected to significantly reduce the absorption of IK-175.
• Uncontrolled or life-threatening symptomatic concomitant disease.
• Clinically significant cardiovascular disease as defined in the protocol.
• Subject is on a medication that is a sensitive substrate of CYP2C8, 2C9, 2C19, or 3A4 that cannot be substituted.
• Females who are pregnant or breastfeeding.

Other inclusion/exclusion criteria are listed in the protocol.