Advanced Melanoma
Conditions
Brief summary
This study will evaluate the efficacy, safety, pharmacokinetics, and patient-reported outcomes (PROs) of autogene cevumeran (RO7198457) plus pembrolizumab compared with pembrolizumab alone in patients with previously untreated advanced melanoma.
Interventions
BIOLOGICALAutogene cevumeran
Participants will receive a recommended dose of autogene cevumeran administered by IV infusion at protocol-defined intervals.
DRUGPembrolizumab
Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W.
Sponsors
Genentech, Inc.
BioNTech SE
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage IIIC or IIID) cutaneous, acral, or mucosal melanoma; * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; * Life expectancy \>/= 12 weeks; * Adequate hematologic and end-organ function; * Naive to prior systemic anti-cancer therapy for advanced melanoma with some exceptions; * Tumor specimen availability; * Measurable disease per RECIST v1.1.
Exclusion criteria
* Ocular/uveal melanoma; * Any anti-cancer therapy with the exceptions as specified in the protocol; * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases; * Previous splenectomy; * History of autoimmune disease; * Prior allogeneic bone marrow transplantation or prior solid organ transplantation; * Positive test for Human Immunodeficiency Virus (HIV) infection; * Active hepatitis B or C or tuberculosis; * Significant cardiovascular disease; * Known clinically significant liver disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) After Randomization | From randomization to PD or death (up to approximately 60 months) | PFS was defined as the time from randomization to the first documented PD as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (KM) method was used to estimate median PFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) According to RECIST V.1.1 After Randomization | Up to approximately 60 months | ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off to the nearest whole number. |
| Overall Survival (OS) After Randomization | From randomization to death (up to approximately 63 months) | OS was defined as the time from randomization to death from any cause. KM method was used to estimate the median OS. |
| Duration of Response (DOR) According to RECIST V.1.1 After Randomization | Up to approximately 60 months | DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD or death from any cause, whichever occurred first, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. DOR was estimated using the KM methodology. |
| Change From Baseline in Global Health Status (GHS)/Health-related Quality of Life (HRQoL) Score Assessed by European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire (EORTC QLQ-C30) | Baseline, Day 1 of Cycles 1 to 34, time of first PD, time to last dose, treatment discontinuation and study drug completion (up to approximately 29 months) (1 cycle = 21 days) | EORTC QLQ-C30 consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding GHS (Question 29: GHS; "How would you rate your overall health during the past week?") and QoL (Question 30: QoL; "How would you rate your overall quality of life during the past week?") and were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized. Scores range from 0-100. A higher score indicates a better QoL. |
| ORR According to RECIST V.1.1 After Crossover | Up to 54.7 months | ORR was defined as the percentage of participants with a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. |
| Number of Participants With Adverse Events (AEs) | Baseline up to 90 days after the final dose of study drug (Safety run-in and randomized stage: up to 32 months; Cross-over stage: up to 24 months) | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. |
Countries
Australia, Belgium, Germany, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 131 participants with previously untreated advanced melanoma took part in the study at 40 investigative sites across the United States, Germany, Australia, Spain, Belgium, and the United Kingdom from 21 December 2018 to 21 January 2025. The study consists of an initial safety run-in stage followed by a randomized stage (Arm A & Arm B). Participants in Arm A had an option to crossover to Arm B after confirmed disease progression (PD), if crossover eligibility criteria were met.
Pre-assignment details
Participants were randomized in a 2:1 ratio to receive either pembrolizumab (Arm A) or pembrolizumab + RO7198457 (Arm B). 1 participant in Arm A did not receive any study treatment and was excluded from safety analysis. 4 participants in Arm B discontinued study treatment after receiving pembrolizumab but prior to receiving RO7198457 & were therefore considered in Arm A for safety analysis.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 124 Participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 6 | 14 / 44 | 30 / 80 | 3 / 10 |
| other Total, other adverse events | 6 / 6 | 40 / 44 | 78 / 80 | 9 / 10 |
| serious Total, serious adverse events | 3 / 6 | 16 / 44 | 25 / 80 | 4 / 10 |
Outcome results
None listed