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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
IK-175 + nivolumab
University of Chicago Medical Center
Chicago, Illinois, United States
Washington University
St Louis, Missouri, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
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 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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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 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
Time frame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 6 months))
Pharmacokinetics (PK) of IK-175 when administered in combination with nivolumab: half-life (t1/2)
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)
PK of IK-175 when administered in combination with nivolumab: area under the plasma concentration-time curve (AUC)
Determine IK-175 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)
Determine IK-175 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)
Determine IK-175 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
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)
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
Time frame: Through study completion including the Treatment Period (approximately 18 months) and the Follow-Up Period (Up to 12 months)