Ph 1/2 Substudy of Oncological Treatment(s) in PD-1 naïve or PD-1 exposed participants with MBM

Phase 1

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

• Registration Number: EUCTR2020-003742-36-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: 2023-02-01
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. AJCC Stage IV (any T, any N, M1D) melanoma
2. Has at least 1 and no more than 5 measurable brain metastasis disease lesions as defined by RECIST 1.1, confirmed by BICR:
-The measurable lesion(s) must be =10 mm and =30 mm in greatest diameter
- Prior SRT in =3 MBM, if there has been complete recovery and there are no neurologic sequelae. Growth or change in any lesion previously irradiated will not be considered measurable for study eligibility but is allowable
- History of excision of =2 melanoma brain metastases if there has been complete recovery and there are no neurologic sequelae. Regrowth in cavity of any previously excised lesion will not be considered measurable for study eligibility but is allowable
- The CIV will confirm this eligibility criterion prior to treatment
randomization/allocation
3. Has provided a tumor biopsy of an extracranial and/or intracranial lesion to confirm histologic or cytologic diagnosis and for biomarker analysis
a) It is strongly preferred that if extracranial disease is present, a tumor sample should be freshly obtained. In cases where newly obtained tissue is not possible to provide or if only intracranial disease is present; an archival sample may be acceptable after discussion with the Sponsor. For participants who have been treated with PD-1/L1 therapy, archival samples that have been obtained after treatment on a PD-1/L1 agent are preferred but not required
b) If a fresh tissue sample is submitted, it is preferred that the tumor biopsy is not obtained from a lone extracranial or intracranial target lesion. If the biopsy specimen was obtained from a lone target lesion, a repeat screening MRI (intracranial lesion) or CT (extracranial lesion) must be obtained postbiopsy and measurable disease confirmed by BICR
4. Neurologically asymptomatic from brain metastases and must not have required or received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
5. Able to undergo MRI with Gadolinium contrast agent
6. Has not received more than 3 lines of therapy for their metastatic melanoma, inclusive of an adjuvant therapy regimen
7. Allowable prior systemic therapy: Previous treatment for unresectable or metastatic disease may include approved adjuvant regimens, IFN-a, anti-PD-1/PD-L1, anti- CTLA-4, and approved molecularly targeted agents. Steroids for physiological replacement are allowed
- Participants who have received anti-PD-1/PD-L1 therapy must have received at least 2 prior doses of an anti-PD-1/L1 mAb
8. Is male or female, from 18 to 120 years of age inclusive, at the time of providing documented informed consent
9. Has an ECOG performance status 0 to 1
10. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
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)
11. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
-A female participant is eligible to participate if she is not pregnant or breastfeeding and at least o

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 10 days before the first dose of study intervention (based upon 5 times the expected half-life of dexamethasone). Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study
2. Current or history of known leptomeningeal involvement. Participants with suspected LMD by clinical symptoms only (without imaging findings) should undergo CSF analysis to substantiate the diagnosis of LMD unless CSF analysis is contraindicated
3. Previous stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing for this study
4. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
5. Untreated or unresolved intracranial hemorrhage from CNS metastasis of more than punctate size on MRI assessment obtained within 28 days prior to study enrollment
6. Has any active infection requiring systemic therapy
7. 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
8. Has ocular melanoma
9. Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another mAb
10. 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
11. Has known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies). No testing of HIV is required unless mandated by local health authority
12. Has known history of hepatitis B (defined as HBsAg reactive) or known hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
13. Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
14. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization/allocation
15. Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If the participant received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity (resolved to = Grade 1) and/or complications from the intervention prior to starting study intervention
16. History of whole brain irradiation
17. Prior treatment with anti-PD-L2, anti-CD137, any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways (except for study interventions noted in inclusion criteria)
18. Has received prior radiotherapy within 2 weeks of first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroid

Study & Design

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