A Study to evaluate the Efficacy and Safety of RO7198457 in Combination With Pembrolizumab Versus Pembrolizumab in Patients with Previously Untreated Advanced Melanoma

Start 26 Feb 2020 · End 22 Jan 2025 · Status Ended · 2 EU/EEA countries · 15 sites · Protocol GO40558

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ended

Participants planned 130

Countries 2

Sites 15

Advanced Melanoma

To evaluate the efficacy of RO7198457 plus pembrolizumab compared with pembrolizumab alone on the basis of progression free survival

Key facts

Sponsor: Genentech Inc.
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Neoplasms [C04]
Trial duration: 26 Feb 2020 → 22 Jan 2025
Decision date (initial): 2024-06-04
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes
Funding sources: Genentech Inc.

External identifiers

EU CT number: 2023-507389-15-00
EudraCT number: 2018-001773-24

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of RO7198457 plus pembrolizumab compared with pembrolizumab alone on the basis of progression free survival

Secondary objectives 2

To evaluate the efficacy of RO7198457 plus pembrolizumab compared with pembrolizumab alone on the basis of Objective Response Rate (ORR), Overall Survival (OS), Duration of Response (DOR), mean change from baseline in Health-Related Quality of Life (HRQoL) scores
To evaluate the safety of RO7198457 plus pembrolizumab compared with pembrolizumab alone on the basis of incidence and severity of adverse events and change from baseline in targeted vital signs and clinical laboratory test results

Conditions and MedDRA coding

Advanced Melanoma

Version	Level	Code	Term	System organ class
21.1	PT	10025670	Malignant melanoma stage III	100000004864
20.0	LLT	10027481	Metastatic melanoma	10029104
21.1	PT	10025671	Malignant melanoma stage IV	100000004864
21.1	PT	10025650	Malignant melanoma	100000004864
20.0	PT	10066600	Melanoma recurrent	100000004864

Study design 3 periods

#	Title	Allocation	Blinding
1	Experimental: Safety Run-in Period: Autogene Cevumeran + Pembrolizumab Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by intravenous (IV) infusion followed by 200 mg pembrolizumab IV infusion every 3 weeks (Q3W) plus a recommended dose of autogene cevumeran.	Randomised Controlled	None
2	Active Comparator: Randomized Period: Arm A: Pembrolizumab Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W. Participants in Arm A have the option to cross over to combination treatment with autogene cevumeran plus pembrolizumab (Arm B) after confirmed disease progression.	Randomised Controlled	None
3	Experimental: Randomized Period: Arm B: Autogene Cevumeran + Pembrolizumab Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by IV infusion followed by 200 mg pembrolizumab IV infusion Q3W plus a recommended dose of autogene cevumeran.	Randomised Controlled	None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

Histologically confirmed metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage IIIC or IIID) cutaneous, acral, or mucosal melanoma, as defined by the AJCC v8.0
ECOG Performance Status of 0 or 1
Life expectancy ≥ 12 weeks
Adequate hematologic and end-organ function
Measurable disease per RECIST v1.1
Naive to prior systemic anti-cancer therapy for advanced melanoma, with the exceptions as specified in the protocol

Exclusion criteria 6

Ocular/uveal melanoma
Known clinically significant liver disease
Previous splenectomy
Any anti-cancer therapy with the exceptions as specified in the protocol
History of autoimmune disease
Positive test for HIV infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival

Secondary endpoints 7

1. Objective Response Rate
2. Overall Survival
3. Duration of Response
4. Mean change from baseline in Health-Related Quality of Life (HRQoL) scores as assessed through use of the two-item Global Health Status (GHS)/HRQoL subscale (Questions 29 and 30) of the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) at specified timepoints
5. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
6. Change from baseline in targeted vital signs
7. Change from baseline in targeted clinical laboratory test results

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

RO7198457

PRD10474694 · Product

Active substance: Autogene Cevumeran
Other product name: Autogene Cevumeran
Pharmaceutical form: CONCENTRATE FOR DISPERSION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1 µg microgram(s)
Max total dose: 1 µg microgram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Not Authorised
MA holder: GENENTECH, INC.
Paediatric formulation: No
Orphan designation: No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323786 · Product

Active substance: Pembrolizumab
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 200 mg milligram(s)
Max total dose: 6.8 g gram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Authorised
ATC code: L01FF02 — -
Marketing authorisation: EU/1/15/1024/002
MA holder: MERCK SHARP & DOHME B.V.
MA country: Norway
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Secondary packaging and labelling for clinical trial use

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genentech Inc.

Sponsor organisation: Genentech Inc.
Address: 1 Dna Way
City: South San Francisco
Postcode: 94080-4918
Country: United States

Scientific contact point

Organisation: Genentech Inc.
Contact name: US Program Manager Product Development Regulatory

Public contact point

Organisation: Genentech Inc.
Contact name: US Program Manager Product Development Regulatory

Third parties 7

Organisation	City, country	Duties
Marken LLP ORG-100048834	Durham, United States	Other
BioNTech SE ORG-100014714	Mainz, Germany	Laboratory analysis
Fortrea Inc. ORG-100012602	Durham, United States	Code 12, Other, Code 5, Code 8
Precision For Medicine Inc. ORG-100041895	Frederick, United States	Laboratory analysis
Labcorp Central Laboratory Services SARL ORG-100011524	Meyrin, Switzerland	Laboratory analysis
DHL Supply Chain Operations GmbH ORG-100040715	Florstadt, Germany	Other
Endpoint Clinical Inc. ORG-100040567	San Francisco, United States	Interactive response technologies (IRT)

Locations

2 EU/EEA countries · 15 investigational sites

By country

Country	MS status	Planned subjects	Sites
Germany	Ended	48	7
Spain	Ended	12	8
Rest of world Australia, United Kingdom, United States	—	70	—

Investigational sites

Germany

7 sites · Ended

Universitat Heidelberg

Dermato-Onkologie, Theodor-Kutzer-Ufer 1-3, Wohlgelegen, Mannheim

University Medical Center Hamburg-Eppendorf

Klinik für Dermatologie und Venerologie, Martinistrasse 52, Eppendorf, Hamburg

Universitaetsklinikum Heidelberg AöR

Dermato-Onkologie, Im Neuenheimer Feld 460, Neuenheim, Heidelberg

Universitaetsklinikum Schleswig-Holstein AöR

Studienzentrum Dermatoonkologie, Ratzeburger Allee 160, 23538, Luebeck

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Onkologisches Studienzentrum, Langenbeckstrasse 1, Oberstadt, Mainz

Universitaetsklinikum Tuebingen AöR

Dept. of Dermatology, Liebermeisterstrasse 25, Innenstadt, Tuebingen

University Hospital Cologne AöR

Tumorzentrum, Kerpener Strasse 62, Lindenthal, Cologne

Spain

8 sites · Ended

Hospital Universitari Vall D Hebron

Oncology, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona

Hospital Universitario Virgen De La Macarena

Oncology, Avenida Del Doctor Fedriani 3, 41009, Sevilla

Hospital Universitario La Paz

Oncology, Paseo Castellana 261, 28046, Madrid

Hospital Clinic De Barcelona

Oncology, Calle Villarroel 170, 08036, Barcelona

Instituto Oncologico Dr. Rosell S.L.

Oncology, Calle De Sabino Arana Num. 5, 08028, Barcelona

Clinica Universidad De Navarra

Oncology, Avenue Pio XII 36, 31008, Pamplona

Hospital General Universitario Gregorio Maranon

Oncology, Calle Del Doctor Esquerdo 46, 28009, Madrid