Ph 1/2 Substudy of 1L Oncological Treatment(s) in Advanced ME

Phase 1

• Conditions: Melanoma; MedDRA version: 21.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003977-24-GR
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-01-30
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

1.Has histologically or cytologically confirmed melanoma.
2.Has unresectable Stage III or Stage IV melanoma, per AJCC 8th Edition Staging Criteria, not amenable to local therapy.
3.Has the presence of at least 1 measurable lesion by CT or MRI per RECIST 1.1 as confirmed by BICR.
a.Cutaneous lesions and other superficial lesions are not considered measurable lesions but may be considered as nontarget lesions.
b.If participants have only 1 measurable lesion per RECIST 1.1, the biopsy specimen should be obtained from the nontarget lesion or archival tissue. If biopsy specimen was obtained from a lone target lesion, a repeat screening CT must be obtained postbiopsy and measurable disease confirmed by BICR.
c.Lesions that are in an area that has been previously irradiated should not be considered measurable unless there has been documented growth of the lesions since the completion of radiation.
4.Has been untreated for advanced disease except as follows:
a.BRAF V600 mutation-positive melanoma may have received SOC targeted therapy as 1L therapy for advanced disease (eg, BRAF/MEK inhibitor, alone or in combination).
b.Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-PD-1 therapy, anti-CTLA-4 or Interferon) is permitted. Prior anti-PD-1 therapy will only be permitted if relapse did not occur during treatment or within 6 months of treatment discontinuation. No other prior adjuvant or neoadjuvant therapy will be allowed.
5.Has documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during Screening (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).
6.Has provided a tumor biopsy.
a.Participants must submit tumor sample during Screening for assessment of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized/allocated.
b.Tumor sample should be freshly obtained (strongly preferred). In cases where newly obtained tissue is not possible to provide; an archival sample may be acceptable.
c.If a fresh tissue sample is submitted, it is preferred that the tumor biopsy is not obtained from a lone target lesion. If the biopsy specimen was obtained from a lone target lesion, a repeat screening CT must be obtained postbiopsy and measurable disease confirmed by BICR.
7.Is male or female from 18 years to 120 years at the time of providing documented informed consent.
8.Has an ECOG performance status 0 to 1 (as assessed within 7 days of the first dose of study intervention).
9. Male participants are eligible to participate if they agree to the following during treatment with the investigational agents.
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
10.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) during the intervention period and for th

Exclusion Criteria

1.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention.
Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, topical steroids, or local steroid injections would not be excluded from the study.
2.Has a known additional malignancy that is progressing or requires active treatment within the past 2 years. Exceptions to the secondary malignancy exclusion include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, new nonulcerated primary melanoma <1 mm in depth with no nodal involvement, Grade 1 follicular lymphoma or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
3.Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated CNS metastases may participate provided they are stable (without evidence of progression by imaging prior to the first dose of study intervention as evidenced by 2 scans at least 4 weeks apart providing stability, and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases confirmed by repeat imaging, and have not required steroids for at least 14 days before study intervention. The second scan showing stability may be used as baseline scan if acquired within the Screening Phase.
Baseline MRI brain scan will be obtained for all participants. Brain CT scan should only be used when MRI is contraindicated. The second brain MRI showing stability may be used as baseline scan if acquired within the Screening Phase.
4.Has ocular or mucosal melanoma.
5.Has known hypersensitivity to active substances or any of their excipients.
6.Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
7.Has an active infection requiring systemic therapy.
8.Has known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies). No testing of HIV is required unless mandated by local health authority.
9.Has known history of hepatitis B (defined as HBsAg reactive) or known hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
10.Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis.
11.Has a history of active tuberculosis (TB; Bacillus tuberculosis).
12.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137, TIGIT).
13.Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization.
14.Has received prior radiotherapy within 2 weeks of the first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
15.Has had major surgery (<3 weeks prior to first dose of study intervention).
16.Has received a live vaccine within 30 days before the first dose of study intervention. E

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified