Combination Therapy With NC-6004 and Pembrolizumab in Head and Neck Cancer Subjects Who Have Failed Platinum Regimen

Study Overview
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Brief Summary
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In Phase IIa, dose-escalation study to determine the optimum tolerated dose and a recommended Phase IIb (RPIIb) dose in combination with pembrolizumab in subjects with recurrent or metastatic squamous cell carcinoma of the head and neck who have failed platinum or a platinum containing regimen. In Phase IIb, randomized control study between NC-6004 in combination with pembrolizumab versus pembrolizumab alone in the same subject population as Part 1 at the RPIIb dose identified in PIIa.

Official Title
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Phase IIa/IIb Clinical Trial of NC-6004 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Have Failed Platinum or a Platinum-containing Regimen

Conditions
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SCCHN

Intervention / Treatment
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* Drug: NC-6004
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to provide written informed consent for the trial. Males or females aged ≥18 years at screening. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Have histologically- or cytologically-confirmed HNSCC. Have recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx that is considered incurable by local therapies. Having prior platinum failure. Exclusion Criteria: Subjects with carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary origination, squamous cell carcinoma that originates from the skin and salivary gland or paranasal sinus, nonsquamous histologies. Have disease that is suitable for locoregional treatment administered with curative intent or refuses curative intent. Have no more than 15% body weight loss due to the underlying condition in the last 3 months from signing of informed consent in Part 1 of the study and from randomization in to Part 2. Are currently participating in or have participated in a study of an investigational agent or are using an investigational device within 4 weeks prior to the first dose of trial treatment. Were previously treated with 3 or more lines of systemic therapies administered for recurrent and/or metastatic disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NC-6004 +pembrolizumab<br>NC-6004 should be administered to subjects once every 3 weeks. On Day 1 of each treatment cycle NC-6004 will be administered first followed by pembrolizumab. In phase IIa portion, NC-6004 dose goes up from 90 mg/m2 up to 135 mg/m2. In phase IIb portion, the dose should be the determined RPII dose in phase IIa portion. | Drug: NC-6004<br>* NC-6004 should be administered to subjects once every 3 weeks. On Day 1 of each treatment cycle NC-6004 will be administered first followed by pembrolizumab.<br>* Other names: Nanoplatin;Drug: Pembrolizumab<br>* The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over 30 minutes every 3 weeks.<br>* Other names: Keytruda;|
| Active Comparator: Pembrolizumab<br>The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over 30 minutes every 3 weeks. | Drug: Pembrolizumab<br>* The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over 30 minutes every 3 weeks.<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Recommended Phase (RPII) dose (mg/m2) of NC-6004 in combination with pembrolizumab | In PIIa portion, to determine RPII dose of NC-6004 in combination with pembrolizumab | 1 year | 
| Compare median Progression Free Survival (PFS) between NC-6004 +pembrolizumab and pembrolizumab alone | In PIIb portion, to compare PFS between NC-6004 plus pembrolizumab and pembrolizumab alone. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare median Overall Survival (OS) between NC-6004 +pembrolizumab and pembrolizumab alone | In PIIb portion, to compare OS rate between NC-6004 plus pembrolizumab and pembrolizumab alone. | 2 years | 
| Compare overall response (complete response and partial response) rate between NC-6004 +pembrolizumab and pembrolizumab alone | In PIIb portion, to ORR between NC-6004 plus pembrolizumab and pembrolizumab alone | 1 year | 
| Compare duration of response between NC-6004 +pembrolizumab and pembrolizumab alone | In PIIb portion, to compare DOR between NC-6004 plus pembrolizumab and pembrolizumab alone | 1 year | 
| Compare time to response between NC-6004 +pembrolizumab and pembrolizumab alone | In PIIb portion, to compare TTR between NC-6004 plus pembrolizumab and pembrolizumab alone | 1 year | 
| Safety and tolerability as measured by severity of Adverse Events (AEs) | The safety endpoints for this study are the incidence and severity of AEs in accordance with the NCI CTCAE and the occurrence of SAEs and treatment discontinuations due to AEs | 1 year | 
| Assess the Maximum Plasma Concentration (Cmax) of NC-6004 in combination with pembrolizumab | Assess PK parameters of the Maximum Plasma Concentration (Cmax) | 1 year | 
| Assess the Time to Maximum Concentration (Tmax) of NC-6004 in combination with pembrolizumab | Assess PK parameters of Time to Maximum Concentration (Tmax) | 1 year | 
| Assess the Area Under the Concentration (AUC) of NC-6004 in combination with pembrolizumab | Assess PK parameters of Area Under the Concentration (AUC) | 1 year | 
| Assess the Half-life(T½) of NC-6004 in combination with pembrolizumab | Assess PK parameters of Half-life(T½) | 1 year | 
| Assess the Clearance (CL) of NC-6004 in combination with pembrolizumab | Assess PK parameters of Clearance (CL) | 1 year | 
| Assess the Volume of Distribution (V) of NC-6004 in combination with pembrolizumab | Assess PK parameters of Volume of Distribution (V) | 1 year |