The purpose of this study is to find out whether treatment with pasritamig and docetaxel prolongs radiographic progression free survival (rPFS) (the length of time from start of treatment until disease worsens as determined by scans) when compared to treatment with docetaxel in participants with metastatic castrate-resistant prostate cancer (mCRPC; a cancer of prostate, a male reproductive gland found below the bladder, that grows despite low levels of male hormones).

A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer

Metastatic Castration-resistant Prostate Cancer

Metastatic Prostate Cancer

Metastatic Castration-resistant Prostate Neoplasms

Metastatic Castration-resistant Prostate Cancer (mCRPC)

Genitourinary Cancer

Advanced Solid Tumors

Prostate Neoplasms

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Prednisone

Docetaxel

Pasritamig

A Phase 3 Randomized, Open-label Study of Pasritamig (JNJ-78278343), a T-cell-redirecting Agent Targeting Human Kallikrein 2, With Docetaxel Versus Docetaxel for Metastatic Castration-resistant Prostate Cancer

rPFS is assessed by BICR and is defined as the time from the date of randomization to the first date of radiographic disease progression, or death due to any cause, whichever occurs first.

OS is defined as the time from the date of randomization to the date of death due to any cause.

TSP is defined as the time from the date of randomization to the date of the first occurrence of any of the following: the use of external beam radiation for skeletal or pelvic symptoms, the need for tumor-related orthopedic surgical intervention, other cancer-related procedures, cancer-related morbid events, and initiation of a new systemic anticancer therapy because of cancer symptoms.

TST is defined as time from randomization to the initiation of any subsequent systemic anticancer therapy.

TSRE is defined as the time from the date of randomization to the date of first occurrence of any of the following: the use of external beam radiation therapy to relieve skeletal symptoms, the need for tumor-related orthopedic surgical intervention, the occurrence of new bone fractures (cancer-related; vertebral or non-vertebral) or the occurrence of tumor-related spinal cord compression.

ORR is defined as the proportion of participants who have measurable disease at baseline and have complete response (CR) or partial response (PR) or better by objective radiographic disease evaluation per response evaluation criteria in solid tumors (RECIST) version.1.1 response criteria and no bone progression as per prostate cancer working group 3 (PCWG3) as determined by the BICR.

DOR will be calculated among responders (PR or better) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3 or RECIST version 1.1 response criteria, or death due to any cause, whichever occurs first.

Time to PSA progression will be calculated from date of enrollment to the date of first documentation of PSA progression. As per Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, PSA progression is defined as greater than or equal to (>=) 25 percent (%) and >=2 nanogram/milliliter (ng/mL) after 12 weeks (in case of no decline in PSA from Baseline), or first PSA increase that is >=25% and >=2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later (in case of decline of PSA from baseline).

PSA-50 response is defined as the proportion of participants with a reduction in blood concentration of PSA (ng/mL) to 50% from baseline, confirmed by a second value.

PSA-90 response is defined as the proportion of participants with a reduction in blood concentration of PSA (ng/mL) to 90% from baseline, confirmed by a second value.

Duration of a PSA response is the time taken to achieve a PSA response that is decrease in PSA from baseline by >= 50%.

PFS2 is defined as the time from randomization to the date of progression (radiographic, clinical, or PSA progression) on the first subsequent anti-cancer (second progression), or death from any cause, whichever comes first.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. An SAE: results in death, is life-threatening, requires inpatient hospitalization or prolonging hospitalization, results in disability, is a congenital birth defect, is a suspected transmission of any infectious agent via a medicinal product, is indicating suicidal ideation, is medically important. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. by using standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; and Grade 5: Death related to AE.

Participants with laboratory abnormalities (hematology, serum chemistry, coagulation, and tumor markers) will be reported.

The BPI-SF was developed to measure both intensity or severity of pain and pain interference with daily life dimensions. It measures pain intensity via 4 questions, that is, "pain at its worst in the last 24 hours", "pain at its least in the last 24 hours", "

The EORTC QLQ-C30 - Version 3 is a self-administered, 30-item questionnaire measuring the health-related quality of life of participants with cancer. EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status / quality of life scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent". A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptom.

The EORTC QLQ-PR25 is a self-completed instrument was specifically designed for prostate cancer patients and includes 25 items that cover 6 dimensions: (1) PR URI (urinary symptoms, 8 items), (2) PR BOW (bowel symptoms, 4 items), (3) PR HTR (hormonal treatment-related symptoms, 6 items), (4) PR AID (incontinence aid, 1 item), (5) PR SAC (sexually active, 2 items); and (6) PR SFU (sexual function, 4 items). Higher scores on symptom domains (for example., urinary, bowel, etc.) indicate greater symptom burden and higher scores on function domains (for example, Sexual Function) indicate better functioning.

The EQ-5D descriptive system comprises 5 items across the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D includes a visual analog scale (EQ-VAS) that has endpoints labeled "best imaginable health state" and "worst imaginable health state" anchored at 100 and 0, respectively. Here, higher score indicates better quality of life.

Time to sustained worsening of pain will be reported using BPI-SF. The BPI-SF was developed to measure both intensity or severity of pain and pain interference with daily life dimensions. It measures pain intensity via 4 questions, that is, "pain at its worst in the last 24 hours", "pain at its least in the last 24 hours", "pain on the average", and "pain you have right now". The BPI-SF assesses how much pain has interfered with the following 7 activities: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Higher score indicates more pain.

The EORTC IL46 is a single question that assesses bother (burden) of treatment. It is rated on a scale from 1 to 4, ranging from "not at all" to "very much".

The EQ-5D descriptive system comprises 5 items across the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D-5L uses a 5-point Likert response scale ranging from "No problems" to "Extreme problems". Here, higher score indicates better quality of life.

Participants will receive pasritamig along with docetaxel until the end of trial (EOT) visit or until confirmed radiographic progression by blinded independent central review (BICR), or any other protocol defined criteria are met.

Participants will receive docetaxel along with prednisone as background medication.

Prostatic Neoplasms, Castration-Resistant

Castration-Resistant Prostatic Cancer

Prostatic Neoplasms

The purpose of this study is to find out whether treatment with pasritamig and docetaxel
prolongs radiographic progression free survival (rPFS) (the length of time from start of
treatment until disease worsens as determined by scans) when compared to treatment with
docetaxel in participants with metastatic castrate-resistant prostate cancer (mCRPC; a
cancer of prostate, a male reproductive gland found below the bladder, that grows despite
low levels of male hormones).

rPFS is assessed by BICR and is defined as the time from the date of randomization to the
first date of radiographic disease progression, or death due to any cause, whichever
occurs first.

OS is defined as the time from the date of randomization to the date of death due to any
cause.

TSP is defined as the time from the date of randomization to the date of the first
occurrence of any of the following: the use of external beam radiation for skeletal or
pelvic symptoms, the need for tumor-related orthopedic surgical intervention, other
cancer-related procedures, cancer-related morbid events, and initiation of a new systemic
anticancer therapy because of cancer symptoms.

TST is defined as time from randomization to the initiation of any subsequent systemic
anticancer therapy.

TSRE is defined as the time from the date of randomization to the date of first
occurrence of any of the following: the use of external beam radiation therapy to relieve
skeletal symptoms, the need for tumor-related orthopedic surgical intervention, the
occurrence of new bone fractures (cancer-related; vertebral or non-vertebral) or the
occurrence of tumor-related spinal cord compression.

ORR is defined as the proportion of participants who have measurable disease at baseline
and have complete response (CR) or partial response (PR) or better by objective
radiographic disease evaluation per response evaluation criteria in solid tumors (RECIST)
version.1.1 response criteria and no bone progression as per prostate cancer working
group 3 (PCWG3) as determined by the BICR.

DOR will be calculated among responders (PR or better) from the date of initial
documentation of a response (PR or better) to the date of first documented evidence of
progressive disease, as defined in the PCWG3 or RECIST version 1.1 response criteria, or
death due to any cause, whichever occurs first.

Time to PSA progression will be calculated from date of enrollment to the date of first
documentation of PSA progression. As per Prostate Cancer Clinical Trials Working Group
(PCWG2) criteria, PSA progression is defined as greater than or equal to (>=) 25 percent
(%) and >=2 nanogram/milliliter (ng/mL) after 12 weeks (in case of no decline in PSA from
Baseline), or first PSA increase that is >=25% and >=2 ng/mL above the nadir, and which
is confirmed by a second value 3 or more weeks later (in case of decline of PSA from
baseline).

PSA-50 response is defined as the proportion of participants with a reduction in blood
concentration of PSA (ng/mL) to 50% from baseline, confirmed by a second value.

PSA-90 response is defined as the proportion of participants with a reduction in blood
concentration of PSA (ng/mL) to 90% from baseline, confirmed by a second value.

Duration of a PSA response is the time taken to achieve a PSA response that is decrease
in PSA from baseline by >= 50%.

PFS2 is defined as the time from randomization to the date of progression (radiographic,
clinical, or PSA progression) on the first subsequent anti-cancer (second progression),
or death from any cause, whichever comes first.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical
(investigational or non investigational) product. An AE does not necessarily have a
causal relationship with the treatment. An SAE: results in death, is life-threatening,
requires inpatient hospitalization or prolonging hospitalization, results in disability,
is a congenital birth defect, is a suspected transmission of any infectious agent via a
medicinal product, is indicating suicidal ideation, is medically important. Severity of
AEs will be graded according to the National Cancer Institute Common Terminology Criteria
for Adverse Events (NCI-CTCAE) v5.0. by using standard grades as follows: Grade 1: Mild;
asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive
intervention indicated; Grade 3: Severe but not immediately life threatening;
hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening
consequences; and Grade 5: Death related to AE.

Participants with laboratory abnormalities (hematology, serum chemistry, coagulation, and
tumor markers) will be reported.

The BPI-SF was developed to measure both intensity or severity of pain and pain
interference with daily life dimensions. It measures pain intensity via 4 questions, that
is, "pain at its worst in the last 24 hours", "pain at its least in the last 24 hours",
"pain on the average", and "pain you have right now". The BPI-SF assesses how much pain
has interfered with the following 7 activities: general activity, mood, walking ability,
normal work, relations with other people, sleep, and enjoyment of life. Higher score
indicates more pain.

The EORTC QLQ-C30 - Version 3 is a self-administered, 30-item questionnaire measuring the
health-related quality of life of participants with cancer. EORTC QLQ-C30 includes 5
functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales
(fatigue, pain, and nausea and vomiting), a global health status / quality of life scale,
and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and
financial difficulties). Responses to items 1-28 are rated on a 4-point Likert response
scale ranging from 1 "Not at all" to 4 "Very much". Two global health status items are
rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent". A high score
for a functional scale represents a high level of functioning, whereas a high score for a
symptom scale/single item represents a high level of symptom.

The EORTC QLQ-PR25 is a self-completed instrument was specifically designed for prostate
cancer patients and includes 25 items that cover 6 dimensions: (1) PR URI (urinary
symptoms, 8 items), (2) PR BOW (bowel symptoms, 4 items), (3) PR HTR (hormonal
treatment-related symptoms, 6 items), (4) PR AID (incontinence aid, 1 item), (5) PR SAC
(sexually active, 2 items); and (6) PR SFU (sexual function, 4 items). Higher scores on
symptom domains (for example., urinary, bowel, etc.) indicate greater symptom burden and
higher scores on function domains (for example, Sexual Function) indicate better
functioning.

The EQ-5D descriptive system comprises 5 items across the following 5 dimensions:
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D
includes a visual analog scale (EQ-VAS) that has endpoints labeled "best imaginable
health state" and "worst imaginable health state" anchored at 100 and 0, respectively.
Here, higher score indicates better quality of life.

Time to sustained worsening of pain will be reported using BPI-SF. The BPI-SF was
developed to measure both intensity or severity of pain and pain interference with daily
life dimensions. It measures pain intensity via 4 questions, that is, "pain at its worst
in the last 24 hours", "pain at its least in the last 24 hours", "pain on the average",
and "pain you have right now". The BPI-SF assesses how much pain has interfered with the
following 7 activities: general activity, mood, walking ability, normal work, relations
with other people, sleep, and enjoyment of life. Higher score indicates more pain.

The EORTC IL46 is a single question that assesses bother (burden) of treatment. It is
rated on a scale from 1 to 4, ranging from "not at all" to "very much"

The EQ-5D descriptive system comprises 5 items across the following 5 dimensions:
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The
EQ-5D-5L uses a 5-point Likert response scale ranging from "No problems" to "Extreme
problems". Here, higher score indicates better quality of life.

Participants will receive pasritamig along with docetaxel until the end of trial (EOT)
visit or until confirmed radiographic progression by blinded independent central review
(BICR), or any other protocol defined criteria are met.

Virginia Cancer Specialists

Liga Norte Riograndense Contra O Cancer

West China Hospital Sichuan University

IRCCS Ospedale San Raffaele

Severance Hospital Yonsei University Health System

Chu Helora Hospital La Louviere Site Jolimont

Beijing Cancer Hospital

Azienda Ospedaliero Universitaria Careggi

Kanazawa University Hospital

Kitasato University Hospital

Yokohama City University Medical Center

Hospital Wanita dan Kanak-Kanak Sabah

Pantai Hospital Kuala Lumpur

Pan American Center for Oncology Trials LLC

National Cancer Center

Samsung Medical Center

A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer

Trials at a glance

Trials at a glance

A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer

Outcome measures

Primary outcome measures

Secondary outcome measures