4SC-202 in Combination With Pembrolizumab in Patients Primary Refractory/Non-responding to Prior Anti-PD-1 Therapy (SENSITIZE)

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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Melanoma
• Intervention / Treatment: Drug: 4SC-202 in combination with Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany
    • Universitätsklinikum Essen
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Universitätsklinikum Heidelberg
  • München, Germany
    • Klinikum der Universität München
  • Tübingen, Germany
    • Universitatsklinikum Tubingen
  • Würzburg, Germany
    • Universitatsklinikum Wurzburg
• Italy
  • Napoli, Italy
    • Istituto Nazionale Tumori Fondazione "G. Pascale"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 4SC-202 + Pembrolizumab; Single arm study of 4SC-202 in combination with Pembrolizumab	Drug: 4SC-202 in combination with Pembrolizumab; 4SC-202 in combination with Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events [Safety and Tolerability]	Safety and tolerability of the combination of 4SC-202 and Pembrolizumab will be assessed from adverse events.	Up to 114 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The Objective Response Rate (ORR) will be defined as the percentage of patients who have achieved a confirmed response of at least Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR)	Up to 102 weeks
Best Overall Response (BOR)	The Best Overall Response defined as the best among all confirmed overall responses (irCR is better than irPR is better than irSD)	Up to 102 weeks
Disease Control Rate (DCR)	The Disease Control Rate (DCR) will be defined as the percentage of patients who have achieved a confirmed response of at least irCR or irPR or a response of irSD	Up to 102 weeks
Duration of Response (DOR)	Duration of response (DOR) is defined as the time from the first documentation of response to the date of disease progression. Patients who have no documented disease progression at the end of the study or who are lost to follow-up or who receive additional anti-neoplastic therapy after discontinuing 4SC-202 and Pembrolizumab will be censored at the date of their last extent of disease assessment or on the first date of additional therapy, respectively.	Up to 102 weeks
Progression Free Survival (PFS)	The time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first). Patients who have not progressed while on study and have not died while on study will be censored at the last evaluable assessment date.	Up to 102 weeks
Time to Progression (TTP)	The time from first dosing (C1D1) to first date of first observed progression. Patients who have not progressed while on study, have not died while on study or experienced a non-disease- related death will be censored at the last evaluable assessment date.	Up to 102 weeks
Overall Survival (OS)	The Overall Survival (OS) is defined as the time from first dosing (C1D1) to date of death from any cause. Patients who have not died while on study will be censored at the last evaluable assessment date	Up to 102 weeks

Collaborators and Investigators

• Sponsor: 4SC AG
• Investigators: Principal Investigator: Dirk Schadendorf, MD, Universitätsklinikum Essen

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 25, 2017
• Primary Completion (ACTUAL): February 2, 2022
• Study Completion (ACTUAL): February 2, 2022

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (ACTUAL): September 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2022
• Last Update Submitted That Met QC Criteria: February 3, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Cutaneous melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: 4SC-202-2-2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No