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History of Changes for Study: NCT04303169
Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C)
Latest version (submitted October 28, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 9, 2020 None (earliest Version on record)
2 March 13, 2020 Study Description, Study Status and Study Identification
3 April 2, 2020 Study Status
4 April 22, 2020 Eligibility and Study Status
5 June 23, 2020 Recruitment Status, Study Status and Contacts/Locations
6 July 2, 2020 Study Status and Contacts/Locations
7 July 10, 2020 Study Status
8 July 29, 2020 Contacts/Locations and Study Status
9 August 5, 2020 Study Status and Contacts/Locations
10 August 20, 2020 Contacts/Locations and Study Status
11 August 27, 2020 Contacts/Locations and Study Status
12 September 4, 2020 Study Status and Contacts/Locations
13 September 10, 2020 Contacts/Locations and Study Status
14 September 23, 2020 Contacts/Locations and Study Status
15 September 30, 2020 Contacts/Locations and Study Status
16 October 8, 2020 Study Status and Contacts/Locations
17 October 16, 2020 Contacts/Locations and Study Status
18 October 21, 2020 Contacts/Locations and Study Status
19 November 5, 2020 Study Status and Contacts/Locations
20 November 12, 2020 Contacts/Locations and Study Status
21 November 23, 2020 Study Identification, Outcome Measures and Study Status
22 December 2, 2020 Contacts/Locations and Study Status
23 December 10, 2020 Arms and Interventions, Eligibility and Study Status
24 December 23, 2020 Contacts/Locations and Study Status
25 February 11, 2021 Study Status and Contacts/Locations
26 March 4, 2021 Study Status and Contacts/Locations
27 March 25, 2021 Contacts/Locations and Study Status
28 April 16, 2021 Study Status and Contacts/Locations
29 June 11, 2021 Study Status and Contacts/Locations
30 June 18, 2021 Contacts/Locations and Study Status
31 June 24, 2021 Contacts/Locations and Study Status
32 July 2, 2021 Study Status and Contacts/Locations
33 August 12, 2021 Study Status and Contacts/Locations
34 August 20, 2021 Contacts/Locations and Study Status
35 August 25, 2021 Contacts/Locations and Study Status
36 September 23, 2021 Study Status and Contacts/Locations
37 October 7, 2021 Study Status and Contacts/Locations
38 October 20, 2021 Contacts/Locations and Study Status
39 November 2, 2021 Study Status and Contacts/Locations
40 November 18, 2021 Contacts/Locations and Study Status
41 December 27, 2021 Arms and Interventions, Study Status, Eligibility and Study Design
42 February 8, 2022 Contacts/Locations and Study Status
43 June 16, 2022 Study Status and Contacts/Locations
44 July 14, 2022 Study Status and Contacts/Locations
45 August 2, 2022 Arms and Interventions, Study Status, References and Eligibility
46 August 19, 2022 Contacts/Locations and Study Status
47 August 26, 2022 Contacts/Locations and Study Status
48 September 2, 2022 Contacts/Locations and Study Status
49 September 15, 2022 Contacts/Locations and Study Status
50 October 13, 2022 Study Status and Contacts/Locations
51 October 28, 2022 Arms and Interventions, Eligibility and Study Status
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Study NCT04303169
Submitted Date:  March 9, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: 3475-02C
Brief Title: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C)
Official Title: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYNOTE-U02): Substudy 02C
Secondary IDs: 2019-003978-22 [EudraCT Number]
MK-3475-02C [Merck]
Open or close this module Study Status
Record Verification: March 2020
Overall Status: Not yet recruiting
Study Start: April 27, 2020
Primary Completion: April 3, 2030 [Anticipated]
Study Completion: April 3, 2030 [Anticipated]
First Submitted: March 9, 2020
First Submitted that
Met QC Criteria:
March 9, 2020
First Posted: March 10, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
March 9, 2020
Last Update Posted: March 10, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary:

Substudy 02C is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study KEYNOTE U02.

The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

Detailed Description:
Open or close this module Conditions
Conditions: Melanoma
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
Coxsackievirus A21
Intracellular Adhesion Molecule-1 (ICAM-1)
T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domains (TIGIT)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 65 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Pembrolizumab + MK-7684

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus MK-7684 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®
Biological: MK-7684
Administered via IV infusion at a specified dose on specified days
Experimental: Pembrolizumab + V937

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus V937 intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®
Biological: V937
Administered via IT injection at a specified dose on specified days
Other Names:
  • Coxsackievirus A21 (CVA21)
  • Formerly known as CAVATAK®
  • CAV21
Experimental: Pembrolizumab

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Biological: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other Names:
  • MK-3475
  • KEYTRUDA®
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percentage of participants who experience an adverse event (AE)
[ Time Frame: Up to ~16 months ]

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.
2. Percentage of participants who discontinue study treatment due to an AE
[ Time Frame: Up to ~12 months ]

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
3. Pathological complete response (pCR) rate
[ Time Frame: Up to ~1.5 months ]

pCR rate is defined as the proportion of participants with complete absence of viable tumor in the treated tumor bed. Assessments are according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by central review of the pathology results. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Secondary Outcome Measures:
1. Near pathological complete response (near pCR) rate
[ Time Frame: Up to ~1.5 months ]

Near pCR is defined as the proportion of participants with >0% but ≤10% of viable tumor cells in the treated tumor bed. Assessments are according to RECIST 1.1 by central review of the pathology results. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
2. Pathological partial response (pPR) rate
[ Time Frame: Up to ~1.5 months ]

pPR rate is defined as the proportion of participants with >10% but ≤50% of the treated tumor bed occupied by viable tumor cells. Assessments are according to RECIST 1.1 by central review of the pathology results. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
3. Recurrence-free survival (RFS)
[ Time Frame: Up to ~65 months ]

RFS is defined as the time from the date of surgery to (1) any recurrence (local, regional, or distant) as assessed by the investigator or (2) death due to any cause (both cancer and noncancer causes of death). Assessments are according to RECIST 1.1 which has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 120 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Has histologically or cytologically confirmed melanoma
  • Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
  • Has been untreated for Stage IIIB, IIIC or IIID melanoma
    • surgical resection of primary melanoma is allowed
    • prior radiotherapy to the primary melanoma is allowed
  • Has provided a baseline tumor biopsy
  • Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of study intervention
  • Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of study intervention
  • Has adequate organ function
  • Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)

Exclusion Criteria:

  • Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
  • Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has ocular or mucosal melanoma
  • Has known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has an active infection requiring systemic therapy
  • Has known history of human immunodeficiency virus (HIV)
  • Has known history of hepatitis B
  • Has a history of (noninfectious) pneumonitis
  • Has a history of active tuberculosis (TB)
  • Has received prior systemic anticancer therapy within 4 weeks prior to randomization
  • Has received prior radiotherapy within 2 weeks of first dose of study intervention
  • Has had major surgery <3 weeks prior to first dose of study intervention
  • Has received a live vaccine within 30 days before the first dose of study intervention
  • Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
  • Has had an allogeneic tissue/solid organ transplant
  • Has only mucosal lesions
  • Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Supporting Information:
Time Frame:
Access Criteria:
URL: http://engagezone.msd.com/ds_documentation.php
Open or close this module References
Citations:
Links:
Available IPD/Information:

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