Clinical trial NCT04991740: A Study of JNJ-78306358 in Participants With Advanced Stage Solid Tumors
Official title: A Phase 1 Study of JNJ-78306358, a T Cell Redirecting Bispecific Antibody Targeting HLA-G for Advanced Stage Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Kidney cancer
Ovarian cancer
Colorectal cancer
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-08-05
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: Inclusion Criteria

* Histologically or cytologically confirmed, metastatic or unresectable solid tumor of one of the following types:

  a. 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
* 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
* 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; c. 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
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
* Selected participants in pharmacokinetics/pharmacodynamic (PK/PD) cohorts and in Part 2 must agree to undergo the mandatory tumor biopsies

Exclusion Criteria:

* Active central nervous system involvement
* 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
* Solid organ or bone marrow transplantation

Primary outcomes:
measure: Number of Participants with Incidence of Adverse Events (AEs)
timeFrame: Up to 2 years and 4 months
measure: Number of Participants with AEs by Severity
timeFrame: Up to 2 years and 4 months
measure: Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Up to 21 days
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of JNJ-78306358
timeFrame: Up to 2 years and 4 months
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-78306358
timeFrame: Up to 2 years and 4 months
measure: Area Under the Serum Concentration-time Curve From Time t1 to t2 (AUC[t1-t2]) of JNJ-78306358
timeFrame: Up to 2 years and 4 months
measure: Accumulation Ratio (RA) of JNJ-78306358
timeFrame: Up to 2 years and 4 months
measure: Number of Participants with Anti-JNJ-78306358 Antibodies
timeFrame: Up to 2 years and 4 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years and 4 months
measure: Duration of Response (DOR)
timeFrame: Up to 2 years and 4 months
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Barcelona
country: Spain
facility: Hosp. Univ. Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. Fund. Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp. Univ. Hm Sanchinarro
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: