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

• ClinicalTrials.gov Identifier: NCT03278665
• Recruitment Status: Completed
• First Posted: September 12, 2017
• Last Update Posted: February 4, 2022
• Sponsor: 4SC AG
• Information provided by (Responsible Party): 4SC AG

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malignant Melanoma	Drug: 4SC-202 in combination with Pembrolizumab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 25, 2017
• Actual Primary Completion Date: February 2, 2022
• Actual Study Completion Date: February 2, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Up to 102 weeks ]
   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)
2. Best Overall Response (BOR) [ Time Frame: Up to 102 weeks ]
   The Best Overall Response defined as the best among all confirmed overall responses (irCR is better than irPR is better than irSD)
3. Disease Control Rate (DCR) [ Time Frame: Up to 102 weeks ]
   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
4. Duration of Response (DOR) [ Time Frame: Up to 102 weeks ]
   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.
5. Progression Free Survival (PFS) [ Time Frame: Up to 102 weeks ]
   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.
6. Time to Progression (TTP) [ Time Frame: Up to 102 weeks ]
   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.
7. Overall Survival (OS) [ Time Frame: Up to 102 weeks ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

Universitätsklinikum Essen

Essen, Germany

Medizinische Hochschule Hannover

Hannover, Germany

Universitätsklinikum Heidelberg

Heidelberg, Germany

Klinikum der Universität München

München, Germany

Universitätsklinikum Tübingen

Tübingen, Germany

Universitätsklinikum Würzburg

Würzburg, Germany

Italy

Istituto Nazionale Tumori Fondazione "G. Pascale"

Napoli, Italy

Sponsors and Collaborators

4SC AG

Investigators

• Principal Investigator: Dirk Schadendorf, MD; Universitätsklinikum Essen

More Information

• Responsible Party: 4SC AG
• ClinicalTrials.gov Identifier: NCT03278665
• Other Study ID Numbers: 4SC-202-2-2017
• First Posted: September 12, 2017
• Last Update Posted: February 4, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by 4SC AG:

Cutaneous melanoma

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action