Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

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.

NC-6004

Cisplatin PEG-pGlu polymeric micelles

IVT

10 mg/ml, 5ml/ vial

Primary Outcome Measures :
Determine the Recommended Phase (RPII) dose (mg/m2) of NC-6004 in combination with pembrolizumab [ Time Frame: 1 year ]
In PIIa portion, to determine RPII dose of NC-6004 in combination with pembrolizumab

Compare median Progression Free Survival (PFS) between NC-6004 +pembrolizumab and pembrolizumab alone [ Time Frame: 1 year ]
In PIIb portion, to compare PFS between NC-6004 plus pembrolizumab and pembrolizumab alone.


Secondary Outcome Measures :
Compare median Overall Survival (OS) between NC-6004 +pembrolizumab and pembrolizumab alone [ Time Frame: 2 years ]
In PIIb portion, to compare OS rate between NC-6004 plus pembrolizumab and pembrolizumab alone.

Compare overall response (complete response and partial response) rate between NC-6004 +pembrolizumab and pembrolizumab alone [ Time Frame: 1 year ]
In PIIb portion, to ORR between NC-6004 plus pembrolizumab and pembrolizumab alone

Compare duration of response between NC-6004 +pembrolizumab and pembrolizumab alone [ Time Frame: 1 year ]
In PIIb portion, to compare DOR between NC-6004 plus pembrolizumab and pembrolizumab alone

Compare time to response between NC-6004 +pembrolizumab and pembrolizumab alone [ Time Frame: 1 year ]
In PIIb portion, to compare TTR between NC-6004 plus pembrolizumab and pembrolizumab alone

Safety and tolerability as measured by severity of Adverse Events (AEs) [ Time Frame: 1 year ]
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

Assess the Maximum Plasma Concentration (Cmax) of NC-6004 in combination with pembrolizumab [ Time Frame: 1 year ]
Assess PK parameters of the Maximum Plasma Concentration (Cmax)

Assess the Time to Maximum Concentration (Tmax) of NC-6004 in combination with pembrolizumab [ Time Frame: 1 year ]
Assess PK parameters of Time to Maximum Concentration (Tmax)

Assess the Area Under the Concentration (AUC) of NC-6004 in combination with pembrolizumab [ Time Frame: 1 year ]
Assess PK parameters of Area Under the Concentration (AUC)

Assess the Half-life(T½) of NC-6004 in combination with pembrolizumab [ Time Frame: 1 year ]
Assess PK parameters of Half-life(T½)

Assess the Clearance (CL) of NC-6004 in combination with pembrolizumab [ Time Frame: 1 year ]
Assess PK parameters of Clearance (CL)

Assess the Volume of Distribution (V) of NC-6004 in combination with pembrolizumab [ Time Frame: 1 year ]
Assess PK parameters of Volume of Distribution (V)

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.