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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05472506
• Other study ID #: IK175-002
• Status: Withdrawn
• Phase: Phase 1
• Start date: March 2023
• Est. completion date: April 2023

Study information

• Verified date: March 2024
• Source: Ikena Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Head and Neck Cancer
• Head and Neck Neoplasms
• Head and Neck Squamous Cell Carcinoma
• Head Cancer
• Head Cancer Neck
• Neck Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• IK-175 + nivolumab
IK-175 + nivolumab

Locations

Country	Name	City	State
United States	University of Chicago Medical Center	Chicago	Illinois
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Ikena Oncology	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Pharmacokinetics (PK) of IK-175 when administered in combination with nivolumab: half-life (t1/2)	Determine IK-175 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)
Secondary	PK of IK-175 when administered in combination with nivolumab: area under the plasma concentration-time curve (AUC)	Determine IK-175 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)
Secondary	PK of IK-175 when administered in combination with nivolumab: maximum serum concentration (Cmax)	Determine IK-175 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)
Secondary	PK of IK-175 when administered in combination with nivolumab: minimum serum concentration (Cmin)	Determine IK-175 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)
Secondary	Preliminary antitumor activity of IK-175 in combination with nivolumab: Progression-free survival (PFS) median and at 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	Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months)
Secondary	Preliminary antitumor activity of IK-175 in combination with nivolumab: Overall survival (OS), median and at 6 months	OS is defined as the length of time from the beginning of study treatment to the date of death due to any cause	Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months)