Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as JNJ-63723283
Cetrelimab · 6 trials · 6 indications
Time from randomization to the first BI-EFS event includes histologically proven presence of muscle-invasive bladder cancer (MIBC), clinical evidence of nodal or metastatic disease (as assessed by RECIST 1.1 criteria), radical cystectomy (RC), or death due to any cause.
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, hematological toxicity, pulmonary toxicity, liver enzyme elevation, treatment delay greater than (\>) 28 days due to unresolved toxicity, or immune-related toxicity requiring the use of therapies in excess of corticosteroids.
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as per investigator assessment.
Cmax is defined as maximum observed serum concentration of cetrelimab.
AUC(0-last) is defined as area under the concentration-time curve from time 0 to the time of the last measurable concentration (non-below quantification limit \[non-BQL\]) of cetrelimab as calculated by linear-linear trapezoidal summation.
t1/2 is defined as apparent terminal elimination half-life of cetrelimab.
Total systemic clearance is a quantitative measure of the rate at which cetrelimab is removed from the body.
The DLTs are based on drug-related adverse events and defined as any of the following events: Infusion-related reactions, non-hematologic toxicity of Grade 3 or higher, or certain hematologic toxicity.
Severity of DLT will be graded by using NCI-CTCAE, version 4.03. Severity scale ranges from Grade 1 to Grade 5 with Grades as follows: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death).
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Severity of AEs will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Any AE not listed in the NCI CTCAE will be graded according to the investigator clinical judgment by using the standard grades as follows: Grade 1 Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 Moderate: Sufficient discomfort is present to cause interference with normal activity; Grade 3 Severe: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to the AE.
Percentage of participants with baseline in PSA level response (greater than or equal to \[\>=\]50 percent \[%\] decrease from baseline in PSA) will be reported at Week 12.
Frequency and severity of dose-limiting toxicity will be reported.
Objective Response Rate (ORR) is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.
AUC (0-tau) is defined as area under the serum concentration versus time curve from time zero to dosing interval.
| Arm | Type | Description |
|---|---|---|
| TAR-200 + Cetrelimab | EXPERIMENTAL | Participants will receive intravesical TAR-200 every 3 weeks (21 days indwelling) for first 18 weeks and thereafter from Week 24 every 12 weeks through study Year 3 in combination with intravenous (IV) Cetrelimab. |
| Chemotherapy (cisplatin or gemcitabine) + Radiation Therapy | ACTIVE_COMPARATOR | Participants will receive chemotherapy based on investigator's choice from either cisplatin intravenously once weekly for 4 to 6 treatment weeks or gemcitabine intravenously twice weekly for 4 to 6 treatment weeks as Standard of Care (SOC) along with radiation therapy from either conventional radiotherapy (64 Gray \[Gy\], bladder only) for up to 6.5 treatment weeks or hypo-fractionated radiotherapy (55 Gy, bladder only) for up to 4 weeks. |
| Phase 1 (Combination Dose Selection) | EXPERIMENTAL | Participants will receive amivantamab low dose or high dose intravenous (IV) infusion based on body weight from Cycle 1 Day 1, Day 2, and subsequently Day 8, Day 15, and Day 22 and then every 2 weeks from Cycle 2 in combination with cetrelimab IV infusion from Cycle 1 Day 2 (after the Day 2 infusion of amivantamab). Cetrelimab treatment duration will be limited to a maximum of 24 months. Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET). Participants who continue to benefit from study treatment(s), as determined by their investigator, may continue to receive access to study treatment(s) within the study by transferring to a long term extension (LTE) phase. |
| Phase 2 (Dose Expansion) | EXPERIMENTAL | Participants will receive amivantamab in combination with cetrelimab in Cohorts A and B at the RP2CD determined by the SET in Phase 1. Participants will continue study treatment until disease progression, unacceptable toxicity, or until another criterion for discontinuation of study treatment is met. Cetrelimab treatment duration will be limited to a maximum of 24 months. Participants who continue to benefit from study treatment(s), as determined by their investigator, may continue to receive access to study treatment(s) within the study by transferring to an LTE phase. |
| Cohort 1: Cetrelimab or Placebo (Dose 1) | EXPERIMENTAL | Participants will receive cetrelimab Dose 1 or placebo via subcutaneous (SC) injection on Day 1. |
| Cohort 2 (Optional): Cetrelimab or Placebo (Dose 2) | EXPERIMENTAL | Participants will receive cetrelimab Dose 2 or placebo administered via an Intravenous (IV) infusion on Day 1 based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as pharmacokinetic (PK) and receptor occupancy (RO) data through at least day 4 postdose). |
| Cohort 3 (Optional): Cetrelimab or Placebo | EXPERIMENTAL | Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose). |
| Cohort 4 (Optional): Cetrelimab or Placebo | EXPERIMENTAL | Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohorts (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose). |
| Phase 1a: JNJ-63723283 (Monotherapy) | EXPERIMENTAL | Participants will receive monotherapy of JNJ-63723283 intravenously. The subsequent dose levels of JNJ-63723283 will be escalated using Bayesian logistic regression model (BLRM). |
| Phase 1b: Erdafitinib Combination | EXPERIMENTAL | Participants will receive erdafitinib in combination with JNJ-63723283 which will be escalated using BLRM. |
| Cohort 1 | EXPERIMENTAL | Biomarker-negative or biomarker-unknown participants with adenocarcinoma (and not treatment-emergent small-cell neuroendocrine prostate cancer \[t-SCNC\]) who progressed on abiraterone acetate plus prednisone/prednisolone (AA-P) will be enrolled in this cohort. Participants will receive cetrelimab 480 milligram (mg) plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days). |
| Cohort 2 | EXPERIMENTAL | Biomarker-negative or biomarker-unknown participants with adenocarcinoma (and not t-SCNC) who progressed on apalutamide, darolutamide, or enzalutamide will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1. |
| Cohort 3 | EXPERIMENTAL | Biomarker-positive participants who progressed on AA-P will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days). |
| Cohort 4 | EXPERIMENTAL | Biomarker-positive participants who progressed on apalutamide, darolutamide, or enzalutamide will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days). |
| Cohort 5 | EXPERIMENTAL | Biomarker-negative participants with t-SCNC who progressed on treatment with AA-P, apalutamide, darolutamide, or enzalutamide will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days). |
| JNJ-63723283 | EXPERIMENTAL | In Part 1, the first cohort will receive JNJ-63723283 at a starting dose of 80 milligram (mg), intravenous (IV) every 2 weeks. JNJ-63723283 doses will be escalated following a modified Continual Reassessment Method (mCRM). Multiple doses, dose administration routes (subcutaneous \[SC\] or IV), and dose schedules may be explored. In Part 2, participants will receive JNJ-63723283 at the recommended Phase 2 dose (RP2D) determined in Part 1. In Part 3, participants will receive JNJ-63723283 to evaluate pharmacokinetic (PK), pharmacodynamic (PD) and safety. In Part 4, participants will receive JNJ-63723283 at the dose level determined in Part 3. Additional cohorts may be enrolled in Part 4. |
| Name | Type | Description |
|---|---|---|
| Cetrelimab | BIOLOGICAL | Participants will receive intravenous Cetrelimab. |
| TAR-200 | DRUG | Participants will receive intravesical TAR-200. |
| Cisplatin | DRUG | Participants will receive cisplatin intravenously. |
| Gemcitabine | DRUG | Participants will receive gemcitabine intravenously. |
| Conventional radiation therapy | RADIATION | Participants will receive conventional radiation therapy for bladder (64 gy). |
| Hypo-fractioned radiation therapy | RADIATION | Participants will receive hypo-fractioned radiation therapy for bladder (55 gy). |
| Amivantamab | DRUG | Amivantamab will be administered as IV infusion. |
| Placebo | DRUG | Placebo will be administered via SC injection or as an IV infusion. |
| JNJ-63723283 | DRUG | JNJ-63723283 will be administered intravenously. |
| Erdafitinib | DRUG | Erdafitinib will be administered orally. |
| Cetrelimab 480 mg | DRUG | Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W). |
| Apalutamide 240 mg | DRUG | Apalutamide 240 mg (4\*60 mg) tablets per day will be administered orally. |
Inclusion Criteria: * Ineligible for or have elected not to undergo radical cystectomy * All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (\<) 2 prior to randomiz...
Cetrelimab is an investigational monoclonal antibody developed by Johnson & Johnson (ticker JNJ). It is being studied in oncology and chronic hepatitis B, including non-small cell lung cancer, castration-resistant prostate cancer, and urinary bladder neoplasms. It is not yet approved and remains in clinical development.
Cetrelimab targets PDCD1, also known as programmed cell death protein 1 (PD-1). It is a PD-1 inhibitor, meaning it blocks this receptor to interfere with a pathway that tumors use to suppress immune responses. This mechanism is intended to restore antitumor immune activity.
Cetrelimab is developed by Johnson & Johnson, which trades under the ticker JNJ. The company is responsible for its clinical development across the studied indications.
Cetrelimab is in Phase 1 development overall, though one Phase 3 trial is evaluating it in combination with TAR-200 in muscle-invasive bladder cancer. It is investigational and has not been approved by the FDA for any indication.
Cetrelimab has been studied in several trials, including NCT05908734 in metastatic non-small cell lung cancer, NCT05242445 in chronic hepatitis B, NCT04658862 in muscle-invasive bladder cancer, and NCT03551782 in metastatic castration-resistant prostate cancer. These trials span Phase 1 to Phase 3 and have enrolled participants across multiple countries.