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

Primary Purpose

Malignant Melanoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
4SC-202 in combination with Pembrolizumab
Sponsored by
4SC AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Melanoma focused on measuring Cutaneous melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Universitätsklinikum Essen
  • Medizinische Hochschule Hannover
  • Universitätsklinikum Heidelberg
  • Klinikum der Universität München
  • Universitätsklinikum Tübingen
  • Universitätsklinikum Würzburg
  • Istituto Nazionale Tumori Fondazione "G. Pascale"

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

4SC-202 + Pembrolizumab

Arm Description

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

Outcomes

Primary Outcome Measures

Incidence of Adverse Events [Safety and Tolerability]
Safety and tolerability of the combination of 4SC-202 and Pembrolizumab will be assessed from adverse events.

Secondary Outcome Measures

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)
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)
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
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.
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.
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.
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

Full Information

First Posted
September 5, 2017
Last Updated
February 3, 2022
Sponsor
4SC AG
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1. Study Identification

Unique Protocol Identification Number
NCT03278665
Brief Title
4SC-202 in Combination With Pembrolizumab in Patients Primary Refractory/Non-responding to Prior Anti-PD-1 Therapy
Acronym
SENSITIZE
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

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
September 25, 2017 (Actual)
Primary Completion Date
February 2, 2022 (Actual)
Study Completion Date
February 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
4SC AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
Keywords
Cutaneous melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
4SC-202 + Pembrolizumab
Arm Type
Experimental
Arm Description
Single arm study of 4SC-202 in combination with Pembrolizumab
Intervention Type
Drug
Intervention Name(s)
4SC-202 in combination with Pembrolizumab
Intervention Description
4SC-202 in combination with Pembrolizumab
Primary Outcome Measure Information:
Title
Incidence of Adverse Events [Safety and Tolerability]
Description
Safety and tolerability of the combination of 4SC-202 and Pembrolizumab will be assessed from adverse events.
Time Frame
Up to 114 weeks
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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)
Time Frame
Up to 102 weeks
Title
Best Overall Response (BOR)
Description
The Best Overall Response defined as the best among all confirmed overall responses (irCR is better than irPR is better than irSD)
Time Frame
Up to 102 weeks
Title
Disease Control Rate (DCR)
Description
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
Time Frame
Up to 102 weeks
Title
Duration of Response (DOR)
Description
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.
Time Frame
Up to 102 weeks
Title
Progression Free Survival (PFS)
Description
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 Frame
Up to 102 weeks
Title
Time to Progression (TTP)
Description
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.
Time Frame
Up to 102 weeks
Title
Overall Survival (OS)
Description
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
Time Frame
Up to 102 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk Schadendorf, MD
Organizational Affiliation
Universitätsklinikum Essen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsklinikum Essen
City
Essen
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
Country
Germany
Facility Name
Klinikum der Universität München
City
München
Country
Germany
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
Country
Germany
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
Country
Germany
Facility Name
Istituto Nazionale Tumori Fondazione "G. Pascale"
City
Napoli
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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