Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)-China Extension

TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product-limit K-M method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

The Prostate-specific Antigen (PSA) response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response. The analysis was performed on participants who had baseline PSA measurements. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG). Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

DOR was the time from first evidence of complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease [NED] on bone scan per PCWG) or partial response (PR: ≥30% decrease in the sum of diameters of target lesions per RECIST 1.1; non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG) until progressive disease (PD) or death. PD per RECIST 1.1 was ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan that were confirmed to not represent tumor flare and persisted for ≥6 weeks. DOR was calculated using the product-limit K-M method. Participants who did not progress were censored at last disease assessment. Per protocol final analysis for this outcome measure was done with the primary completion data cutoff.

TTPP was time from randomization to pain progression (PP) per BPI-SF Item 3 and AQA score. BPI-SF assesses pain intensity; for item 3, responses to "Please rate your pain at its worst in the last 24 hours" are scored from 0 (no pain) to 10 (worst pain). A higher score indicates greater pain. AQA captures the intensity of analgesic use, scored from 0 (no use) to 7 (strong opioid use). A higher score indicates higher intensity of use.

For participants asymptomatic at baseline, PP was ≥2-point change from baseline in Item 3 score OR opioid use initiation. For those symptomatic at baseline, PP was ≥2-point change from baseline in Item 3 score, a score of ≥4, no decrease in average opioid use OR any increase in opioid use (e.g. 1 point change in AQA score). TTPP was assessed by product-limit K-M method. Participants with >2 consecutive unevaluable visits were censored at last assessment. Per protocol final analysis for this outcome measure was done with the primary completion data cutoff.

SSRE was the time from randomization to the first symptomatic skeletal-related event defined as: 1. use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms 2. occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral) 3. occurrence of spinal cord compression 4. tumor-related orthopedic surgical intervention, whichever occurs first. The SSRE was calculated using the product-limit K-M method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

The time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of: 1. ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR 2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline. Time to PSA progression was calculated using the product-limit K-M method for censored data. Participants without PSA progression were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit K-M method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff. The number of participants who experienced an AE is presented.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff. The number of participants who discontinued study treatment due to an AE is presented.