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CompletedNCT03278665SENSITIZEUpdated Feb 4, 2022

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

A Phase 1/2 interventional study of 4SC-202 in combination with Pembrolizumab in Malignant Melanoma, sponsored by 4SC AG. Completed at 7 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-02-04.

Sponsored by 4SC AG · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
40
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

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Conditions studied

  • Malignant Melanoma

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Keywords

  • Cutaneous melanoma
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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
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
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Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    4SC-202 + Pembrolizumab

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

    Drug: 4SC-202 in combination with Pembrolizumab

Interventions

  • Drug4SC-202 in combination with Pembrolizumab

    4SC-202 in combination with Pembrolizumab

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What researchers measure

Primary outcomes

  1. Incidence of Adverse Events [Safety and Tolerability]

    Safety and tolerability of the combination of 4SC-202 and Pembrolizumab will be assessed from adverse events.

    Time frame: Up to 114 weeks

Secondary outcomes

  1. 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)

    Time frame: Up to 102 weeks

  2. 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)

    Time frame: Up to 102 weeks

  3. 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

    Time frame: Up to 102 weeks

  4. 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.

    Time frame: Up to 102 weeks

  5. 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 frame: Up to 102 weeks

  6. 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.

    Time frame: Up to 102 weeks

  7. 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

    Time frame: Up to 102 weeks

06

Study locations

7 sites
  • 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
  • Istituto Nazionale Tumori Fondazione "G. Pascale"
    Napoli, Italy
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References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03278665
Lead sponsor
4SC AG
Responsible party
Sponsor
First posted
Sep 12, 2017
Start date
Sep 25, 2017
Primary completion
Feb 2, 2022
Completion
Feb 2, 2022
Last update
Feb 4, 2022

Study contacts

Dirk Schadendorf, MD
principal investigator · Universitätsklinikum Essen

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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