Head and Neck Squamous Cell CarcinomaPhase 1NCT05472506
Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer
A Phase 1 study testing IK-175 + nivolumab in people with Head and Neck Squamous Cell Carcinoma and Head and Neck Cancer, run by Ikena Oncology at 4 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer, Head Cancer
- What is being tested?
- IK-175 + nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2023to Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Chicago Medical Center
Chicago, Illinois, 60637
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Washington University
St Louis, Missouri, 63130
About this study
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
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.
Read the 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.
- Conditions
- Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer, Head Cancer, Neck Cancer, Head Cancer Neck, Neck Carcinoma
- Being tested
- IK-175 + nivolumab
- 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
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IK-175 + nivolumabDrug
IK-175 + nivolumab
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 600 mg qd PO IK-175 + nivolumab Receives: Drug: IK-175 + nivolumab |
| Cohort 2 | Experimental | 450 mg q12h PO IK-175 + nivolumab Receives: Drug: IK-175 + nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Determine IK-175 half-life (t1/2)
Measured: 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)
Determine IK-175 AUC
Measured: 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)
Determine IK-175 Cmax
Measured: 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)
Determine IK-175 Cmin
Measured: 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
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
Measured: 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 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
Measured: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2022
- Study startMar 2023 (estimated)
- Primary completionApr 2023 (estimated)
- Study completionApr 2023 (estimated)
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized 1:1 to Cohort 1 or Cohort 2
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ikena Oncology
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Katherine Kim, MD, Study director, Ikena OncologyKarim Malek, MD, Study chair, Ikena Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05472506
- Sponsor's protocol ID
- IK175-002
- Status last verified
- Mar 2024
- First submitted
- 20 Jul 2022
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05472506
- Acronym / sponsor ID
- IK175-002
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor Decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ikena OncologyIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- Mar 2023 (estimated)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 25 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized 1:1 to Cohort 1 or Cohort 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: IK-175 + nivolumab600 mg qd PO IK-175 + nivolumab |
| Cohort 2 | Experimental | Drug: IK-175 + nivolumab450 mg q12h PO IK-175 + nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IK-175 + nivolumabIK-175 + nivolumab | Drug | Cohort 1, Cohort 2 |
Primary outcome
Frequency and severity of treatment emergent adverse events (TEAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability]
Time frame: 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]
Time frame: 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]
Time frame: 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]
Time frame: 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)
Time frame: 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)
Time frame: 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
Preliminary antitumor activity of IK-175 treatment in combination with nivolumab: Duration of response (DOR)
Time frame: 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
6 secondary outcomes
Pharmacokinetics (PK) of IK-175 when administered in combination with nivolumab: 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)
PK of IK-175 when administered in combination with nivolumab: area under the plasma concentration-time curve (AUC)
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)
PK of IK-175 when administered in combination with nivolumab: maximum serum concentration (Cmax)
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)
PK of IK-175 when administered in combination with nivolumab: minimum serum concentration (Cmin)
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)
Preliminary antitumor activity of IK-175 in combination with nivolumab: Progression-free survival (PFS) median and at 6 months
Time frame: 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 in combination with nivolumab: Overall survival (OS), median and at 6 months
Time frame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
- Individual participant dataSharing planned: No
Related trials for Head and Neck Squamous Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Not yet recruiting
Tumoral Versus Luminal Microbiome in Head and Neck Squamous Cell Carcinoma
Squamous Cell Cancer of Head and Neck (SCCHN)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Kim, MD study director
Ikena Oncology
Karim Malek, MD study chair
Ikena Oncology
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IK-175 + nivolumab in people with Head and Neck Squamous Cell Carcinoma and Head and Neck Cancer, run by Ikena Oncology at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and severity of treatment emergent adverse events (TEAEs) in subjects receiving IK-175 in combination with nivolumab [Safety and Tolerability] (time frame: Treatment Period (Approximately 18 months)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.