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

NCT05472506 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: IK175-002
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (7)

• Frequency and severity of treatment emergent adverse events (TEAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]

  Number and severity of TEAEs as assessed by CTCAE 5.0

  Treatment Period (Approximately 18 months)

• Frequency and severity of treatment related adverse events (TRAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]

  Number and severity of TRAEs as assessed by CTCAE 5.0

  Treatment Period (Approximately 18 months)

• Frequency and severity of serious adverse events (SAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]

  Number and severity of SAEs as assessed by CTCAE 5.0

  Treatment Period (Approximately 18 months)

• 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]

  Number and severity of adverse events leading to dose modifications and/or treatment discontinuation as assessed by CTCAE 5.0

  Study Treatment Period (Approximately 18 months)

• Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Objective response rate (ORR)

  ORR is defined as the percentage of participants with confirmed complete response (cCR) or confirmed partial response (cPR) per RECIST 1.1

  Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)

• Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Disease control rate (DCR)

  DCR is defined as the percentage of participants with no occurrence of progressive disease with either cCR, cPR, or stable disease \[SD\] ≥ 16 weeks per RECIST 1.1 from the beginning of study therapy

  Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)

• Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Duration of response (DOR)

  DOR is defined as the time from the first documented CR or PR per RECIST 1.1 until disease progression or death from any cause

  Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months))

Secondary Outcomes (6)

• Pharmacokinetics (PK) of IK-175 when administered in combination with nivolumab: half-life (t1/2)

  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)

• PK of IK-175 when administered in combination with nivolumab: area under the plasma concentration-time curve (AUC)

  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)

• PK of IK-175 when administered in combination with nivolumab: maximum serum concentration (Cmax)

  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)

• PK of IK-175 when administered in combination with nivolumab: minimum serum concentration (Cmin)

  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)

• Preliminary antitumor activity of IK-175 in combination with nivolumab: Progression-free survival (PFS) median and at 6 months

  Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)

Study Arms (2)

Cohort 1

EXPERIMENTAL

600 mg qd PO IK-175 + nivolumab

Drug: IK-175 + nivolumab

Cohort 2

EXPERIMENTAL

450 mg q12h PO IK-175 + nivolumab

Drug: IK-175 + nivolumab

Interventions

IK-175 + nivolumab DRUG

IK-175 + nivolumab

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ikena Oncology: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Katherine Kim, MD

  Ikena Oncology

  STUDY DIRECTOR

• Karim Malek, MD

  Ikena Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized 1:1 to Cohort 1 or Cohort 2

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 25, 2022
• Study Start: March 1, 2023
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)