Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)

For participants with confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in sum of diameters of target lesions) as assessed by BICR per modified RECIST; or, for participants with prostate cancer, per PCWG-modified RECIST 1.1 (CR: soft tissue CR with NED on bone scan; PR: soft tissue PR with non-progressive disease, NE, or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan) DOR was defined as time from first documented CR or PR to progressive disease (PD) or death. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also PD. Per PCWG, PD was ≥2 new bone lesions (not tumor flare) persisting ≥6 weeks. DOR is presented.

OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. OS will be reported for all participants.

PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) as assessed by BICR per modified RECIST 1.1 or PCWG-modified RECIST 1.1 (for participants with prostate cancer), or death due to any cause, whichever occurred first. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per PCWG, PD was ≥2 new bone lesions, confirmed to not represent tumor flare, and persistent for ≥6 weeks. The PFS per modified RECIST 1.1/PCWG-modified RECIST 1.1 as assessed by BICR is presented.

An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.

An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be reported.

ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: soft tissue CR with NED on bone scan; PR: soft tissue PR with non-progressive disease, NE, or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan). Per protocol, RECIST 1.1 was modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ. Per protocol, the secondary ORR outcome measure analysis for HRRm positive participants in Cohort 1 (BRCA 1/2) \& Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined, is presented here. Per protocol, Cohort 1 \& 2 were combined as a pre-specified secondary efficacy analysis population.

ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: soft tissue CR with NED on bone scan; PR: soft tissue PR with non-progressive disease, NE, or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan). Per protocol, RECIST 1.1 was modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ. Per protocol, the secondary ORR outcome measure analysis for HRD+ participants in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined, is presented here. Per protocol, Cohort 1 and Cohort 2 were combined as a pre-specified secondary efficacy analysis population.

ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: soft tissue CR with no evidence of disease [NED] on bone scan; PR: soft tissue PR with non-progressive disease, non-evaluable [NE], or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan). Per protocol, RECIST 1.1 was modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ. Per protocol, the secondary ORR outcome measure analysis for all participants regardless of biomarker status in Cohort 1 (BRCA 1/2) and Cohort 2 ([HRRm, BRCA Non-mutated]; [HRD+, HRR Non-mutated]) combined, is presented here.

For participants with CR (disappearance of all target lesions) or PR (≥30% decrease in sum of diameters of target lesions) as assessed by BICR per modified RECIST; or, for participants with prostate cancer, per PCWG-modified RECIST 1.1 (CR: soft tissue CR with NED on bone scan; PR: soft tissue PR with non-progressive disease, NE, or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan) DOR was defined as time from first documented CR/PR to PD or death. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions \& absolute increase of ≥5 mm or appearance of ≥1 new lesion. Per PCWG, PD was ≥2 new bone lesions (not tumor flare) persisting ≥6 weeks. DOR for HRRm positive participants with CR/PR in Cohort 1 \& 2 combined is presented.

For participants with CR (disappearance of all target lesions) or PR (≥30% decrease in sum of diameters of target lesions) as assessed by BICR per modified RECIST; or, for participants with prostate cancer, per PCWG-modified RECIST 1.1 (CR: soft tissue CR with NED on bone scan; PR: soft tissue PR with non-progressive disease, NE, or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan) DOR was defined as time from first documented CR/PR to PD or death. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions \& absolute increase of ≥5 mm or appearance of ≥1 new lesion. Per PCWG, PD was ≥2 new bone lesions (not tumor flare) persisting ≥6 weeks. DOR for HRD+ participants with CR/PR in Cohort 1 \& 2 combined is presented.

For participants with CR (disappearance of all target lesions) or PR (≥30% decrease in sum of diameters of target lesions) as assessed by BICR per modified RECIST; or, for participants with prostate cancer, per PCWG-modified RECIST 1.1 (CR: soft tissue CR with NED on bone scan; PR: soft tissue PR with non-progressive disease, NE, or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan) DOR was defined as time from first documented CR/PR to PD or death. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions \& absolute increase of ≥5 mm or appearance of ≥1 new lesion. Per PCWG, PD was ≥2 new bone lesions (not tumor flare) persisting ≥6 weeks. DOR for all participants in Cohort 1 \& 2 combined with CR/PR is presented.

OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Per protocol, the secondary OS outcome measure analysis for HRRm positive participants in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined, will be presented. Per protocol, Cohort 1 and Cohort 2 will be combined as a pre-specified secondary efficacy analysis.

OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Per protocol, the secondary OS outcome measure analysis for HRD+ participants in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined, will be presented. Per protocol, Cohort 1 and Cohort 2 will be combined as a pre-specified secondary efficacy analysis.

OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Per protocol, the secondary OS outcome measure analysis for all participants regardless of biomarker status in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined, will be presented. Per protocol, Cohort 1 and Cohort 2 will be combined as a pre-specified secondary efficacy analysis.

PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) as assessed by BICR per modified RECIST 1.1 or PCWG-modified RECIST 1.1 (for participants with prostate cancer), or death due to any cause, whichever occurred first. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per PCWG, PD was ≥2 new bone lesions, confirmed to not represent tumor flare, and persistent for ≥6 weeks. Per protocol, the PFS analysis for HRRm positive participants in Cohort 1 and Cohort 2 combined is presented here.

PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) as assessed by BICR per modified RECIST 1.1 or PCWG-modified RECIST 1.1 (for participants with prostate cancer), or death due to any cause, whichever occurred first. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per PCWG, PD was ≥2 new bone lesions, confirmed to not represent tumor flare, and persistent for ≥6 weeks. Per protocol, the PFS analysis for HRD+ participants in Cohort 1 and Cohort 2 combined is presented here.

PFS was defined as the time from first dose of study treatment to the first documented PD as assessed by BICR per modified RECIST 1.1 or PCWG-modified RECIST 1.1 (for participants with prostate cancer), or death due to any cause, whichever occurred first. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per PCWG, PD was ≥2 new bone lesions, confirmed to not represent tumor flare, and persistent for ≥6 weeks. Per protocol, the PFS analysis for all participants regardless of biomarker status in Cohort 1 \& 2 is presented here.

Time to earliest progression by CA-125 was defined as the time from first dose to progression based on CA-125. For participants with BRCA1/2 non-mutated ovarian cancer only, progression by CA-125 was defined as either CA-125 ≥2× upper limit normal (ULN) on 2 occasions 1 week apart or, for participants with elevated CA-125 (≥ULN) at baseline, ≥2× the nadir value on 2 occasions 1 week apart. Time to earliest progression based on CA-125 is presented.

PSA response was defined as a reduction in PSA level ≥50% from baseline measured twice at least 3 weeks apart. For participants with prostate cancer with baseline PSA measurements available, the PSA response rate as assessed is presented.

PFS2 was defined as the time from the first dose of study medication to subsequent disease progression on next-line treatment or death due to any cause, whichever occurred first, as assessed by the investigator. PFS2 for participants with sBRCAm breast cancer in Cohort 3 will be reported.