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| ID | Type | Description | Link |
|---|---|---|---|
| 64457107CAN1001 | Other Identifier | Janssen Research & Development, LLC | |
| 2016-000969-23 | EudraCT Number |
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The primary purpose of the study is to determine the recommended Phase 2 dose (RP2D) and schedule of JNJ-64457107 when administered intravenously (IV) to participants with advanced stage solid tumors in Part 1 and to further characterize the safety of JNJ-64457107 when administered IV to participants with non-small cell lung cancer (NSCLC), pancreatic cancer and cutaneous melanoma in Part 2.
This study has 2 parts: Dose Escalation (part 1) and Dose Expansion (part 2) which are conducted in 3 phases: Screening Phase (up to 28 days prior to first dose of study drug and includes procedures like electrocardiogram [ECG], serum pregnancy test), Treatment phase (continues until the completion of the End-of-Treatment Visit [30 days after last dose of study drug]) and Post-treatment follow-up phase (continues until the participant has died, is lost to follow-up, or has withdrawn consent or the study ends). In follow-up, participants will continue to be monitored for survival status and subsequent cancer-related therapies until the end of study. Additional bio-markers will be assessed, in an optional sub-study, to define the impact of JNJ-64457107 on innate and adaptive immune responses in tumors. Safety will be monitored throughout the study by Safety Evaluation Team (SET).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JNJ-64457107 | Experimental | In Part 1, the first cohort will receive JNJ-64457107 at a starting dose of 75 microgram per kilogram (mcg/kg). The proposed treatment schedule is intravenous (IV) dosing every 14 days. JNJ-64457107 doses will be escalated following a modified Continual Reassessment Method (mCRM); the JNJ-64457107 dose will be increased by not more than half-logarithmical (3.2-fold) dose increments. Dose escalation will continue until the maximum tolerated dose (MTD) and/or RP2D of JNJ-64457107 are defined or the maximum-administered dose (MAD) has been reached. In Part 2, subjects will receive JNJ-64457107 at the RP2D and regimen determined in Part 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JNJ-64457107 | Drug | JNJ-64457107 administered by IV infusion on Day 1 and 14 of a 28-day cycle. |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose-limiting toxicities (Part 1) | Dose-limiting toxicities will be reviewed as a subset of adverse events that occur within the first 28 days of dosing and meet protocol-specified criteria. | Up to 28 days |
| Incidence of adverse events (Part 1 and 2) | From signing of informed consent form (ICF) until 30 days after last dose of study drug (approximately up to 29 Months) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (ORR) | The ORR is the proportion of participants with confirmed best objective response of complete response (CR) or immune-related CR (irCR). | Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) |
| Duration of Response (DOR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Haifa | Israel | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37830579 | Derived | Andersson H, Sobti A, Jimenez DG, de Coana YP, Ambarkhane SV, Hagerbrand K, Smith KE, Lindstedt M, Ellmark P. Early Pharmacodynamic Changes Measured Using RNA Sequencing of Peripheral Blood from Patients in a Phase I Study with Mitazalimab, a Potent CD40 Agonistic Monoclonal Antibody. Cells. 2023 Sep 27;12(19):2365. doi: 10.3390/cells12192365. | |
| 36538259 |
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| ID | Term |
|---|---|
| C000602878 | mitazalimab |
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For participants who achieve CR or partial response (PR), DOR will be calculated as time from initial response of CR or PR to progressive disease or death due to underlying disease, whichever comes first. |
| Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) |
| Progression-free Survival (PFS) | PFS is defined as the time from first dose of JNJ-64457107 to progressive disease or death due to any cause, whichever occurs first. | Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) |
| Overall Survival (OS) | Overall survival is defined as the time from first dose of JNJ-64457107 to date of death from any cause. | Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) |
| Maximum observed serum concentration (Cmax) of JNJ-64457107 | Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment |
| Time of maximum observed serum concentration (Tmax) of JNJ-64457107 | The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. | Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment |
| Area under the serum concentration versus time curve from time 0 to infinity (AUCinf) of JNJ-64457107 | The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant. | Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment |
| Area under the serum concentration versus time curve from time 0 to the final quantifiable time point (t) [AUC(0-t)] of JNJ-64457107 | Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment |
| Area under the serum concentration versus time curve during a dosing interval (AUCtau) of JNJ-64457107 | Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment |
| Immunogenicity of JNJ-64457107 when administered IV | Detection and characterization of antibodies to JNJ-64457107 | Cycle 1: predose on Day 1; Cycle 2: predose on Day 1; Cycles 3, 4: predose; end of treatment visit |
| Jerusalem |
| Israel |
| Tel Aviv | Israel |
| Madrid | Spain |
| Moreno V, Perets R, Peretz-Yablonski T, Fourneau N, Girgis S, Guo Y, Hellemans P, Verona R, Pendas N, Xia Q, Geva R, Calvo E. A phase 1 study of intravenous mitazalimab, a CD40 agonistic monoclonal antibody, in patients with advanced solid tumors. Invest New Drugs. 2023 Feb;41(1):93-104. doi: 10.1007/s10637-022-01319-2. Epub 2022 Dec 20. |