Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115) (Mk-3475-A07/KEYNOTE-A07).

Amgen

Status and phase: Completed; Phase 2

Conditions: Melanoma

Treatments: Drug: Pembrolizumab; Drug: Talimogene laherparepvec

Study type: Interventional

Funder types: Industry

Identifiers

NCT04068181

2019-001906-61 (EudraCT Number)

20180115

Details and patient eligibility

About

This is a phase 2, open-label, single-arm, multicenter clinical trial designed to evaluate the efficacy and safety of talimogene laherparepvec in combination with pembrolizumab following disease progression on prior anti-programmed cell death protein (anti-PD-1) therapy in unresectable/metastatic melanoma (stage IIIB-IVM1d) or prior anti-PD-1 therapy in the adjuvant setting. Subjects will be treated with talimogene laherparepvec and pembrolizumab until confirmed complete response, disappearance of all injectable lesions, documented confirmed disease progression per modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST), intolerance of study treatment, or 102 weeks from the first dose of talimogene laherparepvec and/or pembrolizumab, whichever occurs first.

Enrollment: 72 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Age ≥ 18 years with histologically confirmed diagnosis of stage IIIB to IVM1d melanoma and for whom surgery is not recommended. Subjects with stage IVM1d disease may be enrolled with up to 3 cerebral metastases, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or gamma knife therapy, with no evidence of progression and not requiring steroids for at least 2 months prior to enrollment.
• Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions.
• Subjects must have had prior treatment (for at least 2 to 3 consecutive cycles within an 8 week period) with a PD-1 inhibitor and have confirmed disease progression (as defined by RECIST v1.1 criteria). The anti-PD-1 therapy must be the immediate prior line of therapy before enrollment and subjects with disease progression on more than 1 line of anti-PD-1 therapy are not eligible.
• ECOG performance status of 0 or 1.
• Adequate hematologic, renal, hepatic, and coagulation function.

Key Exclusion Criteria:

• Subjects considered by the investigator to have rapid clinical progression due to melanoma
• Subjects with prior treatment and disease progression on more than 1 line of anti-PD-1 therapy
• Stage IVM1d subjects must not have greater than 3 cerebral melanoma metastases, or clinically active cerebral melanoma metastases requiring therapy, and/or carcinomatous meningitis regardless of clinical stability.
• Primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states or history of other malignancy within the past 3 years.
• Subjects must not have history or evidence of symptomatic autoimmune glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome requiring systemic treatment in the past 2 years (ie, with use of disease modifying agents, steroids or immunosuppressive agents) except vitiligo or resolved childhood asthma/atopy, or evidence of clinically significant immunosuppression.
• Subjects may not have been previously treated with talimogene laherparepvec or any other oncolytic virus.
• Subjects must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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72 participants in 4 patient groups

Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance

Experimental group

Description:

Includes participants who received anti-PD1 therapy in the locally recurrent/metastatic setting and experienced a best overall response of disease progression or stable disease prior to confirmed disease progression. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Treatment:

Drug: Talimogene laherparepvec

Drug: Pembrolizumab

Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance

Experimental group

Description:

Includes participants who received anti-PD-1 therapy in the locally recurrent/metastatic setting and experienced confirmed disease progression following a complete or partial response on anti-PD-1 therapy. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Treatment:

Drug: Talimogene laherparepvec

Drug: Pembrolizumab

Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 months

Experimental group

Description:

Includes participants who received anti-PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of \< 6 months after starting the adjuvant anti-PD-1 therapy. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Treatment:

Drug: Talimogene laherparepvec

Drug: Pembrolizumab

Cohort 4 - Adjuvant Setting -Disease Free Interval ≥ 6 months

Experimental group

Description:

Includes participants who received anti PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of ≥ 6 months after starting the adjuvant PD-1 inhibitor. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Treatment:

Drug: Talimogene laherparepvec

Drug: Pembrolizumab