Clinical trial NCT03278665: 4SC-202 in Combination With Pembrolizumab in Patients Primary Refractory/Non-responding to Prior Anti-PD-1 Therapy
Official title: An Open-label Phase Ib/II, Multi-center Study of 4SC-202 in Combination With Pembrolizumab in Patients With Unresectable Stage III/Metastatic Stage IV Cutaneous Melanoma Primary Refractory/Non-responding to Prior Anti-PD-1 Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malignant Melanoma
Keywords: Cutaneous melanoma
Lead sponsor: 4SC AG
Sponsor class: INDUSTRY
First posted: 2017-09-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase Ib/II open-label, multi-center study with a priming cycle of 4SC-202 to evaluate the safety, tolerability and preliminary efficacy of combination treatment with 4SC-202 and Pembrolizumab. A dose expansion cohort at the Recommended Phase Two Dose (RPTD) will be added.

Adult patients with advanced (unresectable or metastatic) cutaneous melanoma primary refractory or non-responding to anti-PD-1 therapy as most current systemic anti-cancer therapy and for whom no standard therapy is available, will be enrolled. The last administration of anti-PD-1 therapy must have been performed within 6 months prior to screening.


Eligibility criteria: Main Inclusion Criteria:

* Patients with unresectable stage III or stage IV cutaneous melanoma, as per American Joint Committee on Cancer (AJCC) (Version 8) staging system (must have been histologically confirmed at least once during course of disease). Patients with metastatic tumor of unknown primary site and histology of melanoma are eligible.
* Patients must be primary refractory or non-responding to anti-PD-1 therapy (either as monotherapy or in combination with Ipilimumab)
* Measurable disease by computer tomography (CT) or Magnetic resonance imaging (MRI) per immune-related response evaluation criteria in solid tumors (irRECIST) 1.1 criteria, with longest diameter for non-nodal lesions ≥ 10 mm and ≥ 15 mm in short axis for nodal lesions
* At least one tumor site (either primary site or metastasis) must be accessible for sequential biopsies and patient must consent to the 2 mandatory biopsies. This requirement is not applicable for continuous dosing schedules and may be waived by the sponsor in other individual cases.

Main Exclusion Criteria:

* Patients who achieved a CR or PR, during or after prior anti-PD-1 mono- or anti-CTLA-4/anti-PD-1 combination therapy
* Patients with symptomatic brain metastases/central nervous system (CNS) involvement
* Patients with inadequate organ function
* Therapy with agents known to prolong the QT interval and increase the risk for Torsades de Pointes

Primary outcomes:
measure: Incidence of Adverse Events [Safety and Tolerability]
timeFrame: Up to 114 weeks
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 102 weeks
measure: Best Overall Response (BOR)
timeFrame: Up to 102 weeks
measure: Disease Control Rate (DCR)
timeFrame: Up to 102 weeks
measure: Duration of Response (DOR)
timeFrame: Up to 102 weeks
measure: Progression Free Survival (PFS)
timeFrame: Up to 102 weeks
measure: Time to Progression (TTP)
timeFrame: Up to 102 weeks
measure: Overall Survival (OS)
timeFrame: Up to 102 weeks
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: München
country: Germany
facility: Klinikum der Universität München
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione "G. Pascale"
Study officials:
affiliation: Universitätsklinikum Essen
name: Dirk Schadendorf, MD
role: PRINCIPAL_INVESTIGATOR
References: