A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05116202

Collaborator

(none)

191

Enrollment

Locations

Arms

20.2

Anticipated Duration (Months)

9.6

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Nivolumab Drug: Ipilimumab Drug: RO7247669 Drug: Atezolizumab Drug: Tiragolumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

191 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)

Actual Study Start Date :

Feb 2, 2022

Anticipated Primary Completion Date :

Apr 24, 2023

Anticipated Study Completion Date :

Oct 11, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cohort 1: Nivolumab + Ipilimumab Cohort 1 participants in the nivolumab plus ipilimumab arm will receive treatment for 2 cycles (6 weeks) on Day 1 of each cycle (cycle length 21 days) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	Drug: Nivolumab Nivolumab will be administered at a dose of 3 mg/kg IV on Day 1 of each 21 day cycle. Drug: Ipilimumab Ipilimumab will be administered at a dose of 1 mg/kg by IV on Day 1 of each 21 day cycle.
Experimental: Cohort 1: RO7247669 Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	Drug: RO7247669 RO7247669 will be administered at a dose of 2100 mg by IV infusion on Day 1 of each 21 day cycle.
Experimental: Cohort 1: + Atezolizumab + Tiragolumab Cohort 1 participants in the atezolizumab plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	Drug: Atezolizumab Atezolizumab will be administered at a dose of 1200 mg IV on Day 1 of each 21 day cycle. Other Names: Tecentriq, RO5541267 Drug: Tiragolumab Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle. Other Names: RO7092284
Experimental: Cohort 1: RO7247669 + Tiragolumab Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	Drug: RO7247669 RO7247669 will be administered at a dose of 2100 mg by IV infusion on Day 1 of each 21 day cycle. Drug: Tiragolumab Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle. Other Names: RO7092284
Experimental: Cohort 2: RO7247669 + Tiragolumab Cohort 2 participants in RO7247669 plus tiragolumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.	Drug: RO7247669 RO7247669 will be administered at a dose of 2100 mg by IV infusion on Day 1 of each 21 day cycle. Drug: Tiragolumab Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle. Other Names: RO7092284

Outcome Measures

Primary Outcome Measures

Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review [Time of surgery (Week 7)]
pRR is defined as the proportion of participants with pathologic complete response (pCR), pathologic near complete response (pnCR), and pathologic partial response (pPR) at time of surgery, as determined by independent pathologic review.
Objective Response Rate (ORR) for Cohort 2 [Enrollment/randomization up to approximately 5 years]
ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to RECIST v1.1.

Secondary Outcome Measures

pRR for Cohort 1 as Determined by Local Pathologic Assessment [Time of surgery (Week 7)]
pRR is defined as the proportion of participants with pCR, pnCR, and pPR at time of surgery, as determined by local pathologic assessment.
Event-Free Survival (EFS) for Cohort 1 [Randomization to disease progression that precludes surgery; local, regional or distant disease recurrence; or death from any cause (whichever occurs first) (up to approximately 5 years)]
EFS is defined as the time from randomization to any of the following events (whichever occurs first): Disease progression that precludes surgery, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); local, regional or distant disease recurrence; or death from any cause.
Relapse-Free Survival (RFS) for Cohort 1 [Surgery to the first documented recurrence of disease or death from any cause (up to approximately 5 years)]
RFS is defined as the time from surgery to the first documented recurrence of disease or death from any cause.
Overall Survival (OS) for Cohort 1 [Randomization to death from any cause (up to approximately 5 years)]
OS is defined as the time from randomization to death from any cause.
Objective Response Rate (ORR) for Cohort 1 [Prior to surgery (up to Week 6)]
ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1, prior to surgery.
Percentage of Participants With Adverse Events for Cohort 1 [Baseline through the end of the study (approximately 5 years)]
Percentage of Participants With Immune-Related Adverse Events for Cohort 1 [Baseline to Week 12]
Percentage of participants with immune-related adverse events Grade >= 3 during the first 12 weeks.
Rate of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1 [Week 8 to Week 9]
Duration of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1 [Week 8 to Week 9]
Surgical Complication Rates for Cohort 1 [Week 7 through Follow-Up (up to approximately 6 months)]
Surgical complication rates according to Clavien-Dindo surgical classification after completion lymph node dissection (CLND).
Progression-Free Survival (PFS) for Cohort 2 [Randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)]
PFS after randomization/enrollment, defined as the time from randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Overall Survival (OS) for Cohort 2 [Randomization/enrollment to death from any cause (up to approximately 5 years)]
OS after randomization/enrollment, defined as the time from randomization/enrollment to death from any cause.
Overall Survival (OS) at Specific Timepoints for Cohort 2 [Randomization/enrollment to death from any cause at specific timepoints (up to approximately 5 years)]
OS after randomization/enrollment, defined as the time from randomization/enrollment to death from any cause.
Duration of Response (DOR) for Cohort 2 [First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)]
DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Disease Control for Cohort 2 [Randomization up to approximately 5 years]
Disease control is defined as stable disease for >= 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1.
Percentage of Participants With Adverse Events for Cohort 2 [Baseline through the end of the study (approximately 5 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

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.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	The Angeles Clinic and Research Institute - W LA Office	Los Angeles	California	United States	90025
3	Providence St Johns Health Center	Santa Monica	California	United States	90404
4	Moffitt Cancer Center	Tampa	Florida	United States	33612
5	MD Anderson Cancer Center	Houston	Texas	United States	77030
6	Melanoma Institute Australia	North Sydney	New South Wales	Australia	2060
7	Linear Clinical Research Limited	Nedlands	Western Australia	Australia	6009
8	Hopital de la Timone	Marseille		France	13005
9	APHP - Hospital Saint Louis	Paris		France	75475
10	Institut Universitaire du Cancer de Toulouse-Oncopole	Toulouse		France	31059
11	Institut Gustave Roussy	Villejuif		France	94805
12	Azienda Ospedaliera Universitaria Senese	Siena	Abruzzo	Italy	53100
13	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania	Italy	80131
14	Istituto Europeo Di Oncologia	Milano	Lombardia	Italy	20141
15	Ospedale S.Maria della Misericordia	Perugia	Umbria	Italy	06132
16	Leids Universitair Medisch Centrum	Leiden		Netherlands	2333 ZA
17	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
18	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
19	Clinica Universidad de Navarra ; Servicio de Farmacia	Madrid		Spain	28027
20	Hospital Universitario HM Sanchinarro-CIOCC	Madrid		Spain	28050

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT05116202

Other Study ID Numbers:

BO43328

First Posted:

Nov 10, 2021

Last Update Posted:

Aug 3, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 3, 2022