Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma. (NCT NCT03815058)

Last Updated: 2026-01-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

131 participants

Primary outcome timeframe

From randomization to PD or death (up to approximately 60 months)

Results posted on

2026-01-30

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Safety Run-in Participants received pembrolizumab monotherapy, 200 milligrams (mg) as an intravenous (IV) infusion for at least 1 cycle, followed by pembrolizumab, 200 mg, IV infusion, every 3 weeks (Q3W) thereafter, along with RO7198457. Participants received RO7198457, 25 micrograms (µg), as an IV infusion, 4 doses every week (QW) and 4 doses Q3W as induction dosing and then maintenance dosing every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm A: Pembrolizumab Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
Safety Run-in Stage STARTED	6	0	0	0
Safety Run-in Stage Safety-evaluable (SE) Population	6	0	0	0
Safety Run-in Stage COMPLETED	0	0	0	0
Safety Run-in Stage NOT COMPLETED	6	0	0	0
Randomized Stage STARTED	0	41	84	0
Randomized Stage SE Population	0	44	80	0
Randomized Stage COMPLETED	0	0	0	0
Randomized Stage NOT COMPLETED	0	41	84	0
Cross-over Treatment STARTED	0	0	0	10
Cross-over Treatment SE Population	0	0	0	10
Cross-over Treatment COMPLETED	0	0	0	0
Cross-over Treatment NOT COMPLETED	0	0	0	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Safety Run-in Participants received pembrolizumab monotherapy, 200 milligrams (mg) as an intravenous (IV) infusion for at least 1 cycle, followed by pembrolizumab, 200 mg, IV infusion, every 3 weeks (Q3W) thereafter, along with RO7198457. Participants received RO7198457, 25 micrograms (µg), as an IV infusion, 4 doses every week (QW) and 4 doses Q3W as induction dosing and then maintenance dosing every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm A: Pembrolizumab Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
Safety Run-in Stage Death	2	0	0	0
Safety Run-in Stage Study Ended by Sponsor	4	0	0	0
Randomized Stage Death	0	13	29	0
Randomized Stage Lost to Follow-up	0	2	4	0
Randomized Stage Study Ended by Sponsor	0	14	42	0
Randomized Stage Withdrawal by Subject	0	2	9	0
Randomized Stage Discontinued due to PD to Receive Cross-over Treatment	0	10	0	0
Cross-over Treatment Death	0	0	0	2
Cross-over Treatment Study Ended by Sponsor	0	0	0	7
Cross-over Treatment Withdrawal by Subject	0	0	0	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Run-in n=6 Participants Participants received pembrolizumab monotherapy, 200 mg as an IV infusion for at least 1 cycle, followed by pembrolizumab, 200 mg, IV infusion, Q3W thereafter, along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm A: Pembrolizumab n=41 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 n=84 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Total n=131 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 11.0 • n=35 Participants	62.4 years STANDARD_DEVIATION 14.4 • n=4328 Participants	63.6 years STANDARD_DEVIATION 14.2 • n=8687 Participants	63.2 years STANDARD_DEVIATION 14.0 • n=269 Participants
Sex: Female, Male Female	1 Participants n=35 Participants	11 Participants n=4328 Participants	27 Participants n=8687 Participants	39 Participants n=269 Participants
Sex: Female, Male Male	5 Participants n=35 Participants	30 Participants n=4328 Participants	57 Participants n=8687 Participants	92 Participants n=269 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=35 Participants	1 Participants n=4328 Participants	1 Participants n=8687 Participants	2 Participants n=269 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=35 Participants	39 Participants n=4328 Participants	69 Participants n=8687 Participants	114 Participants n=269 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=35 Participants	1 Participants n=4328 Participants	14 Participants n=8687 Participants	15 Participants n=269 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=35 Participants	0 Participants n=4328 Participants	0 Participants n=8687 Participants	0 Participants n=269 Participants
Race (NIH/OMB) Asian	0 Participants n=35 Participants	0 Participants n=4328 Participants	1 Participants n=8687 Participants	1 Participants n=269 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=35 Participants	0 Participants n=4328 Participants	0 Participants n=8687 Participants	0 Participants n=269 Participants
Race (NIH/OMB) Black or African American	0 Participants n=35 Participants	0 Participants n=4328 Participants	1 Participants n=8687 Participants	1 Participants n=269 Participants
Race (NIH/OMB) White	6 Participants n=35 Participants	38 Participants n=4328 Participants	80 Participants n=8687 Participants	124 Participants n=269 Participants
Race (NIH/OMB) More than one race	0 Participants n=35 Participants	0 Participants n=4328 Participants	0 Participants n=8687 Participants	0 Participants n=269 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=35 Participants	3 Participants n=4328 Participants	2 Participants n=8687 Participants	5 Participants n=269 Participants

PRIMARY outcome

Timeframe: From randomization to PD or death (up to approximately 60 months)

Population: ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Arm A: Pembrolizumab n=41 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 n=84 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) After Randomization	7.9 months Interval 2.8 to 22.7	8.3 months Interval 6.9 to 26.9	—	—

SECONDARY outcome

Timeframe: Up to approximately 60 months

Population: ITT population included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Arm A: Pembrolizumab n=41 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 n=84 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
Objective Response Rate (ORR) According to RECIST V.1.1 After Randomization	48.8 percentage of participants Interval 32.26 to 65.3	41.7 percentage of participants Interval 30.53 to 52.8	—	—

SECONDARY outcome

Timeframe: From randomization to death (up to approximately 63 months)

Population: ITT population included all randomized participants.

OS was defined as the time from randomization to death from any cause. KM method was used to estimate the median OS.

Outcome measures

Outcome measures
Measure	Arm A: Pembrolizumab n=41 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 n=84 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
Overall Survival (OS) After Randomization	NA months Interval 19.6 to The median and upper limit of the 95% confidence interval (CI) were not estimable due to an insufficient number of participants with events.	62.2 months Interval 41.8 to The upper limit of the 95% CI was not estimable due to an insufficient number of participants with events.	—	—

SECONDARY outcome

Timeframe: Up to approximately 60 months

Population: ITT population included all randomized participants. Overall number analyzed is the number of participants with an OR (CR or PR).

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.

Outcome measures

Outcome measures
Measure	Arm A: Pembrolizumab n=20 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 n=35 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
Duration of Response (DOR) According to RECIST V.1.1 After Randomization	NA months Interval 19.8 to The median and upper limit of the 95% CI were not estimable due to an insufficient number of participants with events.	NA months Interval 36.1 to The median and upper limit of the 95% CI were not estimable due to an insufficient number of participants with events.	—	—

SECONDARY outcome

Timeframe: 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)

Population: ITT population included all randomized participants. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Arm A: Pembrolizumab n=39 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 n=83 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
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) Change at Cycle 2 Day 1	-1.85 score on a scale Standard Deviation 17.72	-1.37 score on a scale Standard Deviation 14.40	—	—
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) Change at Cycle 4 Day 1	3.74 score on a scale Standard Deviation 16.45	-3.70 score on a scale Standard Deviation 19.48	—	—
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) Change at Cycle 15 Day 1	0.56 score on a scale Standard Deviation 13.16	-3.07 score on a scale Standard Deviation 16.37	—	—
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	64.74 score on a scale Standard Deviation 24.67	73.39 score on a scale Standard Deviation 21.56	—	—
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) Change at Cycle 1 Day 1	—	0.00 score on a scale Standard Deviation 0.00	—	—
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) Change at Cycle 3 Day 1	2.60 score on a scale Standard Deviation 16.73	0.54 score on a scale Standard Deviation 16.69	—	—
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) Change at Cycle 5 Day 1	3.53 score on a scale Standard Deviation 19.32	-1.84 score on a scale Standard Deviation 15.56	—	—
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) Change at Cycle 6 Day 1	0.00 score on a scale Standard Deviation 20.57	-6.03 score on a scale Standard Deviation 22.51	—	—
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) Change at Cycle 7 Day 1	2.27 score on a scale Standard Deviation 15.04	-1.01 score on a scale Standard Deviation 15.85	—	—
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) Change at Cycle 8 Day 1	0.83 score on a scale Standard Deviation 10.08	0.15 score on a scale Standard Deviation 18.35	—	—
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) Change at Cycle 9 Day 1	-2.92 score on a scale Standard Deviation 12.76	-1.19 score on a scale Standard Deviation 15.77	—	—
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) Change at Cycle 10 Day 1	4.39 score on a scale Standard Deviation 14.26	-3.72 score on a scale Standard Deviation 15.43	—	—
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) Change at Cycle 11 Day 1	0.52 score on a scale Standard Deviation 16.52	1.06 score on a scale Standard Deviation 14.29	—	—
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) Change at Cycle 12 Day 1	1.56 score on a scale Standard Deviation 13.34	-4.07 score on a scale Standard Deviation 14.82	—	—
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) Change at Cycle 13 Day 1	1.11 score on a scale Standard Deviation 24.57	0.00 score on a scale Standard Deviation 13.61	—	—
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) Change at Cycle 14 Day 1	2.98 score on a scale Standard Deviation 12.49	-2.03 score on a scale Standard Deviation 13.54	—	—
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) Change at Cycle 16 Day 1	0.64 score on a scale Standard Deviation 16.12	-1.72 score on a scale Standard Deviation 15.04	—	—
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) Change at Cycle 17 Day 1	4.86 score on a scale Standard Deviation 15.27	-2.60 score on a scale Standard Deviation 15.62	—	—
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) Change at Cycle 18 Day 1	5.00 score on a scale Standard Deviation 18.51	-4.57 score on a scale Standard Deviation 17.72	—	—
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) Change at Cycle 19 Day 1	0.00 score on a scale Standard Deviation 19.64	-1.61 score on a scale Standard Deviation 14.18	—	—
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) Change at Cycle 20 Day 1	5.56 score on a scale Standard Deviation 11.79	-1.67 score on a scale Standard Deviation 14.42	—	—
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) Change at Cycle 21 Day 1	9.26 score on a scale Standard Deviation 12.80	-0.31 score on a scale Standard Deviation 15.41	—	—
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) Change at Cycle 22 Day 1	11.46 score on a scale Standard Deviation 12.55	-1.79 score on a scale Standard Deviation 17.18	—	—
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) Change at Cycle 23 Day 1	8.33 score on a scale Standard Deviation 9.32	-2.68 score on a scale Standard Deviation 17.43	—	—
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) Change at Cycle 24 Day 1	2.78 score on a scale Standard Deviation 13.82	-3.87 score on a scale Standard Deviation 22.28	—	—
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) Change at Cycle 25 Day 1	1.85 score on a scale Standard Deviation 18.53	-4.81 score on a scale Standard Deviation 18.59	—	—
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) Change at Cycle 26 Day 1	5.21 score on a scale Standard Deviation 14.04	-3.40 score on a scale Standard Deviation 14.85	—	—
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) Change at Cycle 27 Day 1	0.00 score on a scale Standard Deviation 8.91	-2.47 score on a scale Standard Deviation 15.64	—	—
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) Change at Cycle 28 Day 1	-4.76 score on a scale Standard Deviation 20.89	-2.67 score on a scale Standard Deviation 17.47	—	—
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) Change at Cycle 29 Day 1	2.08 score on a scale Standard Deviation 14.60	-2.47 score on a scale Standard Deviation 15.98	—	—
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) Change at Cycle 30 Day 1	-1.04 score on a scale Standard Deviation 5.34	-7.69 score on a scale Standard Deviation 17.47	—	—
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) Change at Cycle 31 Day 1	3.13 score on a scale Standard Deviation 14.73	-3.67 score on a scale Standard Deviation 18.65	—	—
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) Change at Cycle 32 Day 1	7.29 score on a scale Standard Deviation 14.39	-3.21 score on a scale Standard Deviation 18.72	—	—
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) Change at Cycle 33 Day 1	5.21 score on a scale Standard Deviation 13.32	-4.81 score on a scale Standard Deviation 18.59	—	—
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) Change at Cycle 34 Day 1	7.29 score on a scale Standard Deviation 13.68	-5.00 score on a scale Standard Deviation 18.16	—	—
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) Change at Time of First PD	-1.47 score on a scale Standard Deviation 26.06	-4.17 score on a scale Standard Deviation 19.43	—	—
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) Change at Time of Last Dose	-5.65 score on a scale Standard Deviation 25.40	-7.30 score on a scale Standard Deviation 23.55	—	—
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) Change at Treatment Discontinuation	-2.27 score on a scale Standard Deviation 26.75	-11.07 score on a scale Standard Deviation 18.43	—	—

SECONDARY outcome

Timeframe: Up to 54.7 months

Population: Crossover ITT population included all randomized participants who entered crossover period.

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.

Outcome measures

Outcome measures
Measure	Arm A: Pembrolizumab n=10 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm B: Pembrolizumab + RO7198457 Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
ORR According to RECIST V.1.1 After Crossover	40.0 percentage of participants Interval 4.64 to 75.36	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: SE population included all participants who received at least 1 dose of study treatment. 1 participant in Arm A didn't receive any study treatment \& was excluded from safety. 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Pembrolizumab n=6 Participants Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	Arm B: Pembrolizumab + RO7198457 n=44 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Arm B: Pembrolizumab + RO7198457 n=80 Participants Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	Crossover: Pembrolizumab + RO7198457 n=10 Participants Participants in Arm A with confirmed PD were given the option to crossover \& receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
Number of Participants With Adverse Events (AEs)	6 Participants	43 Participants	79 Participants	10 Participants

Adverse Events

Safety Run-in

Serious events: 3 serious events

Other events: 6 other events

Deaths: 2 deaths

Arm A: Pembrolizumab

Serious events: 16 serious events

Other events: 40 other events

Deaths: 14 deaths

Arm B: Pembrolizumab + RO7198457

Serious events: 25 serious events

Other events: 78 other events

Deaths: 30 deaths

Crossover: Pembrolizumab + RO7198457

Serious events: 4 serious events

Other events: 9 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER