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

INTERVENTION: Product Code: NC‐6004 Pharmaceutical Form: Solution for infusion INN or Proposed INN: CISPLATIN CAS Number: 1009838‐50‐9 Current Sponsor code: NC‐6004 Other descriptive name: Cisplatin‐PEG‐pGlu Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ Trade Name: KEYTRUDA Product Name: KEYTRUDA Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Pembrolizumab Other descriptive name: L‐HISTIDINE HYDROCHLORIDE Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ CONDITION: Head and neck squamous cell carcinoma (HNSCC) ; MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: ; Main Objective: Part 1(Phase IIa):; To assess dose‐limiting toxicities (DLTs), and to determine the optimal dose in order to establish the recommended Phase IIb (RPIIb) dose for the combination of NC‐6004 plus pembrolizumab.; ; Part 2 (Phase IIb):; To compare progression‐free survival (PFS) between NC‐6004 plus pembrolizumab and pembrolizumab alone.; ; Primary end point(s): ‐ To establish the RPIIb dose.; ‐ To determine the PFS by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in eligible subjects after treatment with NC‐6004 plus pembrolizumab and pembrolizumab alone.; ; Secondary Objective: To evaluate the safety and tolerability of NC‐6004 when combined with pembrolizumab.; To compare OS between NC‐6004 plus pembrolizumab and pembrolizumab alone.; To compare tumor response between NC‐6004 plus pembrolizumab and pembrolizumab alone.; Timepoint(s) of evaluation of this end point: RP2D will be determined in March 2019. PFS in PIIb portion will be available in March 2022. SECONDARY OUTCOME: ; Secondary end point(s): • Overall response rate (ORR) ; • Complete response (CR)/ Partial response (PR) ; • Stable disease (SD) ; • Duration of response (DOR) ; • Time to response (TTR) ; Pharmacokinetics endpoints: ; • Cmax (maximum concentration) ; • Tmax (time to maximum concentration) ; • AUC0‐t (area under the concentration‐time curve from time zero to the end of the dosing interval) ; • AUC0‐8 (area under the concentration‐time curve from time zero to infinity) ; • Rac (Accumulation Ratio) ; • ?z (terminal elimination phase rate constant) ; • T½ (terminal half‐life) ; • CL (clearance) ; • Vz (volume of distribution) ; Safety data as well as PK data of PIIa portion will be available in March 2019. OS or other efficacy data of PIIb will be available in March 2022.; INCLUSION CRITERIA: 1. Be willing and able to provide written informed consent for the trial. 2. Males or females aged =18 years at screening. 3. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 ; • Vss (volume of distribution at steady‐state); ; Timepoint(s) of evaluation of this end point: ORR will be assessed by performing study imaging every 6 weeks after the first dose of study treatment. 4. Have histologically‐ or cytologically‐confirmed HNSCC. 5. 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 6. Must have received = 150mg/m2 of a total dose of cisplatin or 2 cycles of carboplatin AUC5 (maximum carboplatin dose per cycle 750mg) 7. Prior platinum failure as defined by a. Disease progression confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) scans using RECIST 1.1 criteria at any time during o