A Study of JNJ-78306358 in Participants With Advanced Stage Solid Tumors
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the recommended phase 2 dose (RP2D) regimen(s) of JNJ-78306358 in Part 1 (Dose Escalation) and to determine the safety of JNJ-78306358 at the RP2D regimen(s) in Part 2 (Dose Expansion).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
JNJ-78306358 is a bispecific antibody binding to CD3 on T cells and human leukocyte antigen G (HLA-G) on cancer cells. The study consists of a screening phase, a treatment phase, and a post-treatment follow-up phase. Study evaluations include safety, pharmacokinetics, biomarkers, immunogenicity, and efficacy (disease evaluations). The total study duration will be up to 2 years 4 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Dose Escalation Participants with renal cell carcinoma (RCC), ovarian cancer, colorectal cancer (CRC), and other tumor types with sponsor approval will receive JNJ-78306358. The dose will be escalated sequentially based on the decisions of the study evaluation team until the recommended phase 2 dose (RP2D) regimen(s) have been identified. |
Drug: JNJ-78306358
JNJ-78306358 will be administered.
|
| Experimental: Part 2: Dose Expansion Participants with RCC, ovarian cancer, CRC and other types of tumors will receive JNJ-78306358 at the RP2D regimen(s) determined in Part 1. |
Drug: JNJ-78306358
JNJ-78306358 will be administered.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Incidence of Adverse Events (AEs) [Up to 2 years and 4 months]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
- Number of Participants with AEs by Severity [Up to 2 years and 4 months]
Number of participants with AEs by severity will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events, which will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. 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.
- Part 1: Number of Participants with Dose-limiting Toxicity (DLT) [Up to 21 days]
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Secondary Outcome Measures
- Maximum Serum Concentration (Cmax) of JNJ-78306358 [Up to 2 years and 4 months]
Cmax is defined as maximum serum concentration of JNJ-78306358.
- Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-78306358 [Up to 2 years and 4 months]
Tmax is defined as time to reach maximum observed serum concentration of JNJ-78306358.
- Area Under the Serum Concentration-time Curve From Time t1 to t2 (AUC[t1-t2]) of JNJ-78306358 [Up to 2 years and 4 months]
AUC(t1-t2) is defined as the area under the serum concentration-time curve from time t1 to t2.
- Accumulation Ratio (RA) of JNJ-78306358 [Up to 2 years and 4 months]
RA is calculated as area under the plasma concentration-time curve from time zero to 24 hours (AUC [0-24]) value at steady state divided by AUC (0-24) value after first dose.
- Number of Participants with Anti-JNJ-78306358 Antibodies [Up to 2 years and 4 months]
Number of participants with anti-JNJ-78306358 antibodies will be reported.
- Overall Response Rate (ORR) [Up to 2 years and 4 months]
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version 1.1 and gynecological cancer inter group (GCIG) Cancer antigen 125 (CA 125) response criteria (for ovarian cancer participants only).
- Duration of Response (DOR) [Up to 2 years and 4 months]
Duration of response (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 RECIST version 1.1 response criteria and GCIG CA 125 response criteria (for ovarian cancer participants only) or death due to any cause, whichever occurs first.
Eligibility Criteria
Criteria
Inclusion Criteria
- Histologically or cytologically confirmed, metastatic or unresectable solid tumor of one of the following types:
- Renal Cell Carcinoma (RCC): clear cell or papillary carcinoma, b. ovarian cancer: high grade serous epithelial ovarian; primary peritoneal or fallopian tube cancer; 1. low grade or non-serous histologies are not allowed; c. colorectal cancer (CRC); d. other tumor types (including lung adenocarcinoma, endometrial cancer, and pancreas cancer) may be enrolled with sponsor approval
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Measurable or evaluable disease: a. Part 1: either measurable or evaluable disease; b. Part 2: at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Participants with ovarian cancer without a measurable lesion must have disease evaluable per RECIST version1.1 (example ascites) or have Cancer antigen 125 (CA 125) greater than (>) 2*upper limit of normal (ULN) within 2 weeks prior to first dose of study drug
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Progressed during or after the following prior therapies for metastatic disease, unless participant was ineligible to receive them: a) RCC: clear cell histology: an antiangiogenic agent and an immune checkpoint inhibitor, administered as 1 or more lines of therapy. For papillary renal carcinoma 1 line of systemic therapy; b. CRC: at least 2 lines of therapy including a fluoropyrimidine, oxaliplatin, and irinotecan given with or without antiangiogenic therapies or epidermal growth factor receptor (EGFR) antibodies. In addition, prior treatment with anti-programmed cell death protein 1 (PD1) antibody is required for high microsatellite instability (MSI-H) CRC;
- ovarian cancer: at least 2 lines of therapy, including at least 1 line with platinum. Maintenance therapy after completion of platinum-containing regimen, example with bevacizumab or a poly- Adenosine di-phosphate (ADP) ribose polymerase inhibitor will not count as a separate line of therapy; d. other tumor types: at least 2 lines of systemic therapy
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Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
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Selected participants in pharmacokinetics/pharmacodynamic (PK/PD) cohorts and in Part 2 must agree to undergo the mandatory tumor biopsies
Exclusion Criteria:
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Active central nervous system involvement
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Toxicity from prior anticancer therapy has not resolved to baseline levels or to Grade less than or equal to (<=) 1 (except alopecia, vitiligo, peripheral neuropathy, or endocrinopathies that are stable on hormone replacement, which may be Grade 2)
-
Clinically significant pulmonary compromise
-
Autoimmune or inflammatory disease requiring systemic steroids or other immunosuppressive agents (example, methotrexate or tacrolimus) within 1 year prior to first dose of study drug
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Solid organ or bone marrow transplantation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rambam Medical Center | Haifa | Israel | 31096 | |
| 2 | Sourasky Medical Center | Tel Aviv | Israel | 64239 | |
| 3 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 8035 | |
| 4 | Hosp. Univ. Fund. Jimenez Diaz | Madrid | Spain | 28040 | |
| 5 | Hosp. Univ. Hm Sanchinarro | Madrid | Spain | 28050 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR109028
- 2021-001646-35
- 78306358STM1001