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

Primary Purpose

Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer, Head Cancer

Status

Not yet recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

IK-175 + nivolumab

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Chicago Medical Center
Washington University
UPMC Hillman Cancer Center
Seattle Cancer Care Alliance

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Arm Description

600 mg qd PO IK-175 + nivolumab

450 mg q12h PO IK-175 + nivolumab

Outcomes

Primary Outcome Measures

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

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

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

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

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

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

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

Secondary Outcome Measures

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

Determine IK-175 half-life (t1/2)

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

Determine IK-175 AUC

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

Determine IK-175 Cmax

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

Determine IK-175 Cmin

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

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

Full Information

NCT ID

NCT05472506

First Posted

July 20, 2022

Last Updated

September 22, 2022

Sponsor

Ikena Oncology

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT05472506

Brief Title

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

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

September 2022 (Anticipated)

Primary Completion Date

July 2024 (Anticipated)

Study Completion Date

July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ikena Oncology

Collaborators

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

Randomized 1:1 to Cohort 1 or Cohort 2

Masking

None (Open Label)

Masking Description

Open label study

Allocation

Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

600 mg qd PO IK-175 + nivolumab

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

450 mg q12h PO IK-175 + nivolumab

Intervention Type

Drug

Intervention Name(s)

IK-175 + nivolumab

Intervention Description

IK-175 + nivolumab

Primary Outcome Measure Information:

Title

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

Description

Number and severity of TEAEs as assessed by CTCAE 5.0

Time Frame

Treatment Period (Approximately 18 months)

Title

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

Description

Number and severity of TRAEs as assessed by CTCAE 5.0

Time Frame

Treatment Period (Approximately 18 months)

Title

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

Description

Number and severity of SAEs as assessed by CTCAE 5.0

Time Frame

Treatment Period (Approximately 18 months)

Title

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]

Description

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

Time Frame

Study Treatment Period (Approximately 18 months)

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Determine IK-175 half-life (t1/2)

Time Frame

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)

Title

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

Description

Determine IK-175 AUC

Time Frame

Title

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

Description

Determine IK-175 Cmax

Time Frame

Title

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

Description

Determine IK-175 Cmin

Time Frame

Title

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

Description

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

Time Frame

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

Title

Preliminary antitumor activity of IK-175 in combination with nivolumab: Overall survival (OS), median and at 6 months

Description

OS is defined as the length of time from the beginning of study treatment to the date of death due to any cause

Time Frame

Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Marissa Timothy, MS

Phone

(603) 361-8939

mtimothy@ikenaoncology.com

First Name & Middle Initial & Last Name or Official Title & Degree

Jen Schroeder

Phone

(857) 419-6991

jschroeder@ikenaoncology.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Katherine Kim, MD

Organizational Affiliation

Ikena Oncology

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Karim Malek, MD

Organizational Affiliation

Ikena Oncology

Official's Role

Study Chair

Facility Information:

Facility Name

University of Chicago Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ari Rosenberg, MD

Phone

773-702-8222

arirosenberg@medicine.bsd.uchicago.edu

Facility Name

Washington University

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63130

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Douglas Adkins, MD

Phone

314-454-8305

dadkins@wustl.edu

First Name & Middle Initial & Last Name & Degree

Jessica Ley

Phone

(314) 747-8092

jcley@wustl.edu

Facility Name

UPMC Hillman Cancer Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dan P Zandberg, MD

Phone

412-623-8963

zandbergdp@upmc.edu

Facility Name

Seattle Cancer Care Alliance

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Cristina Rodriguez, MD

Phone

206-288-6748

rodrigcr@uw.edu

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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