Clinical trial NCT05472506: Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Head and Neck Squamous Cell Carcinoma
Head and Neck Cancer
Head Cancer
Neck Cancer
Head Cancer Neck
Neck Carcinoma
Keywords: IK-175
AHR antagonist
AHR inhibitor
Aryl Hydrocarbon Receptor Antagonist
Immunooncology
AHRi
Aryl Hydrocarbon Receptor Inhibitor
Antagonist
Inhibitor
anti-PD1
aPD1
nivolumab
checkpoint inhibitor
CPI
combination therapy
Lead sponsor: Ikena Oncology
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2022-07-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 1:1 to Cohort 1 or Cohort 2
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency and severity of treatment emergent adverse events (TEAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
timeFrame: Treatment Period (Approximately 18 months)
measure: Frequency and severity of treatment related adverse events (TRAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
timeFrame: Treatment Period (Approximately 18 months)
measure: Frequency and severity of serious adverse events (SAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
timeFrame: Treatment Period (Approximately 18 months)
measure: Frequency and severity of adverse events leading to dose modifications and/or treatment discontinuation in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
timeFrame: Study Treatment Period (Approximately 18 months)
measure: Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Objective response rate (ORR)
timeFrame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)
measure: Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Disease control rate (DCR)
timeFrame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)
measure: Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Duration of response (DOR)
timeFrame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months))
Secondary outcomes:
measure: Pharmacokinetics (PK) of IK-175 when administered in combination with nivolumab: half-life (t1/2)
timeFrame: Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months)
measure: PK of IK-175 when administered in combination with nivolumab: area under the plasma concentration-time curve (AUC)
timeFrame: Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months)
measure: PK of IK-175 when administered in combination with nivolumab: maximum serum concentration (Cmax)
timeFrame: Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months)
measure: PK of IK-175 when administered in combination with nivolumab: minimum serum concentration (Cmin)
timeFrame: Time Frame: Day 1, 2, 15 of Cycle 1, Day 1 of Cycles 2-3 (every 28 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 56 days) through end of treatment (approximately 18 months)
measure: Preliminary antitumor activity of IK-175 in combination with nivolumab: Progression-free survival (PFS) median and at 6 months
timeFrame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)
measure: Preliminary antitumor activity of IK-175 in combination with nivolumab: Overall survival (OS), median and at 6 months
timeFrame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Ikena Oncology
name: Katherine Kim, MD
role: STUDY_DIRECTOR
affiliation: Ikena Oncology
name: Karim Malek, MD
role: STUDY_CHAIR
References: