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: Recruiting
• First Posted: September 12, 2017
• Last Update Posted: September 14, 2020
• Sponsor: 4SC AG
• Information provided by (Responsible Party): 4SC AG

Tracking Information

• First Submitted Date: September 5, 2017
• First Posted Date: September 12, 2017
• Last Update Posted Date: September 14, 2020
• Actual Study Start Date: September 25, 2017
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 11, 2017)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 11, 2017)

• 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)
• 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)
• 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
• 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.
• 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.
• 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.
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Malignant Melanoma

Intervention

Drug: 4SC-202 in combination with Pembrolizumab

4SC-202 in combination with Pembrolizumab

Study Arms

Experimental: 4SC-202 + Pembrolizumab

Single arm study of 4SC-202 in combination with Pembrolizumab

Intervention: Drug: 4SC-202 in combination with Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 11, 2017): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chief Medical Officer, MD; +49 700 763 ext 0; medical.request@4sc.com

• Listed Location Countries: Germany, Italy

Administrative Information

• NCT Number: NCT03278665
• Other Study ID Numbers: 4SC-202-2-2017
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: 4SC AG
• Study Sponsor: 4SC AG
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dirk Schadendorf, MD; Universitätsklinikum Essen

• PRS Account: 4SC AG
• Verification Date: September 2020