Phase 2
Completed N=110
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
Source: ClinicalTrials.gov NCT05116202 ↗Enrolled (actual)
110
Serious AEs
20.9%
Results posted
Jul 2025
Primary outcomePrimary: Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review — 77.3; 80.0; 45.0; 60.0 percentage of participants
Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of treatment combinations in cancer immunotherapy (CIT)-naive participants with resectable Stage III melanoma (Cohort 1) and in participants with Stage IV melanoma (Cohort 2). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review |
77.3; 80.0; 45.0; 60.0 | — |
| PRIMARY Objective Response Rate (ORR) for Cohort 2 as Determined by the Investigator |
— | — |
| SECONDARY pRR for Cohort 1 as Determined by Local Pathologic Assessment |
81.8; 75.0; 50.0; 60.0 | — |
| SECONDARY Event-free Survival (EFS) for Cohort 1 |
19.55; NA; 22.51; NA | — |
| SECONDARY Relapse-free Survival (RFS) for Cohort 1 |
17.91; 17.08; 20.90; NA | — |
| SECONDARY Overall Survival (OS) for Cohort 1 |
NA; NA; NA; NA | — |
| SECONDARY ORR for Cohort 1 |
59.1; 37.5; 35.0; 60.0 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) for Cohort 1 |
19; 36; 19; 18; 4; 13 | — |
| SECONDARY Number of Participants With Immune-related AEs Grade ≥ 3 for Cohort 1 |
5; 1; 0; 3 | — |
| SECONDARY Rate of Delayed Surgery Due to Treatment-related AEs |
13.6; 2.5; 0; 5.0 | — |
| SECONDARY Duration of Surgery Delay Due to Treatment-related AEs |
17.0; 5.1; 3.0 | — |
| SECONDARY Surgical Complication Rates for Cohort 1 |
0; 0; 5.55; 5.26; 18.18; 5.26 | — |
| SECONDARY Progression-Free Survival (PFS) for Cohort 2 |
2.07 | — |
| SECONDARY OS for Cohort 2 |
8.94 | — |
| SECONDARY OS Rates at Specific Timepoints for Cohort 2 |
100.0; 71.43; 47.62 | — |
| SECONDARY Duration of Response (DOR) for Cohort 2 |
— | — |
| SECONDARY Disease Control Rate (DCR) for Cohort 2 |
— | — |
| SECONDARY Number of Participants With AEs and Severity of AEs Determined According to NCI CTCAE v5.0 for Cohort 2 |
7; 0; 6; 1; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria for Cohort 1:
- ECOG performance status (PS) of 0 or 1
- Histologically confirmed resectable Stage III melanoma according to AJCC-8 and no history of in-transit metastases within the last 6 months
- Fit and planned for CLND
- Measurable disease according to RECIST v1.1
- Availability of a representative tumor specimen
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Negative HIV test, negative hepatitis B surface antibody (HBsAb), and negative total hepatitis B core antibody (HBcAb) test, and negative hepatitis C virus (HCV) at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load.
Exclusion Criteria for Cohort 1:
- Mucosal, uveal and acral lentiginous melanoma
- Distantly metastasized melanoma
- History of in-transit metastases within the last 6 months
- Prior radiotherapy
- Prior immunotherapy, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, and other systemic therapy for melanoma
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
- Prior allogeneic stem cell or solid organ transplantation
- Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication, or anticipation of need for systemic immunosuppressant medication during study treatment
- Active or history of autoimmune disease or immune deficiency
Inclusion Criteria for Cohort 2:
- ECOG PS of 0 or 1
- Life expectancy >= 3 months, as determined by the investigator
- Histologically confirmed Stage IV (metastatic) cutaneous melanoma according to AJCC-8
- Disease progression during or following at least one but no more than two lines of treatment for metastatic disease
- Measurable disease according to RECIST v1.1
- Availability of a representative tumor specimen
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Negative HIV test, negative hepatitis B surface antibody (HBsAb), and negative total hepatitis B core antibody (HBcAb) test, and negative hepatitis C virus (HCV) at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load.
Exclusion Criteria for Cohort 2:
- Mucosal and uveal melanoma
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
- Prior allogeneic stem cell or solid organ transplantation
- Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication, or anticipation of need for systemic immunosuppressant medication during study treatment
- Active or history of autoimmune disease or immune deficiency
- Symptomatic, untreated, or progressing CNS metastases
- Active or history of carcinomatous meningitis/leptomeningeal disease
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled or symptomatic hypercalcemia
Data sourced from ClinicalTrials.gov (NCT05116202). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.