Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Head Cancer, Head Cancer Neck, Neck Cancer, Neck Carcinoma
Conditions
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
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.
Interventions
DRUGIK-175 + nivolumab
IK-175 + nivolumab
Sponsors
Bristol-Myers Squibb
Ikena Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label study
Intervention model description
Randomized 1:1 to Cohort 1 or Cohort 2
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Duration of response (DOR) | Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)) | 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 |
| Frequency and severity of treatment emergent adverse events (TEAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability] | Treatment Period (Approximately 18 months) | Number and severity of TEAEs as assessed by CTCAE 5.0 |
| Frequency and severity of treatment related adverse events (TRAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability] | Treatment Period (Approximately 18 months) | Number and severity of TRAEs as assessed by CTCAE 5.0 |
| Frequency and severity of serious adverse events (SAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability] | Treatment Period (Approximately 18 months) | Number and severity of SAEs as assessed by CTCAE 5.0 |
| 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] | Study Treatment Period (Approximately 18 months) | Number and severity of adverse events leading to dose modifications and/or treatment discontinuation as assessed by CTCAE 5.0 |
| Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Objective response rate (ORR) | Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months) | ORR is defined as the percentage of participants with confirmed complete response (cCR) or confirmed partial response (cPR) per RECIST 1.1 |
| Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Disease control rate (DCR) | Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Determine IK-175 AUC |
| 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) | Determine IK-175 Cmax |
| 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) | Determine IK-175 Cmin |
| 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) | PFS is defined as the length of time from the beginning of study treatment to the first observed disease progression or death due to any cause |
| Preliminary antitumor activity of IK-175 in combination with nivolumab: Overall survival (OS), median and at 6 months | Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months) | OS is defined as the length of time from the beginning of study treatment to the date of death due to any cause |
| 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) | Determine IK-175 half-life (t1/2) |
Countries
United States
Outcome results
None listed