This study has been transitioned to CTIS with ID 2023-506585-31-00 check the CTIS register for the current data. The study contains 2 parts: Part 1 is the dose escalation part. Part 2 is the dose expansion part.The primary objective of part 1 is to…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of part 1 is to determine recommended Phase 2 dose(s)
(RP2Ds) of JNJ-78278343 by investigating the incidence and severity of AEs,
including dose-limiting toxicity.
The primary objective of part 2 is to determine the safety at the RP2D(s) by
investigating the incidence and severity of AEs
Secondary outcome
The secondary objectives are:
-Assess the pharmacokinetics by looking at the serum concentration-time
profiles and pharmacokinetic parameters for JNJ-78278343 including but not
limited to Cmax, Tmax, AUC(t1-t2), AUCtau, Cmin, and accumulation ratio (RA)
- Assess the pharmacodynamics by looking at the pharmacodynamic markers
including, but not limited to, systemic cytokine concentrations and serum PSA
- Assess the immunogenicity by looking at the presence of anti-JNJ-78278343
antibodies
-Assess preliminary antitumor activity by looking at the objective response
rate, PSA response, and duration of response according to response criteria of
the Prostate Cancer Working Group 3 (PCWG3).
Background summary
JNJ-78278343 is a humanized immunoglobulin (Ig)G1-based bispecific antibody
designed to direct T lymphocytes (T cells) to human kallikrein 2 (hK2or KLK2)
positive target tumor cells. One arm of JNJ-78278343 binds to the cluster of
differentiation (CD)3 receptor complex present on T cells and the other arm
binds to KLK2 present on target tumor cells leading to the activation of the T
cells and T-cell-mediated lysis of the KLK2 bearing tumor cells. JNJ-78278343
is being developed for the treatment of metastatic castration-resistant
prostate cancer (mCRPC). KLK2 expression is highly restricted in normal tissues
and highly enriched in prostate adenocarcinoma and its expression is mostly
maintained throughout disease progression, making KLK2 an attractive target for
therapy.
Study objective
This study has been transitioned to CTIS with ID 2023-506585-31-00 check the CTIS register for the current data.
The study contains 2 parts: Part 1 is the dose escalation part. Part 2 is the
dose expansion part.
The primary objective of part 1 is to determine recommended Phase 2 dose(s)
(RP2Ds) of JNJ-78278343 by investigating the incidence and severity of AEs,
including dose-limiting toxicity.
The primary objective of part 2 is to determine the safety at the RP2D(s) by
investigating the incidence and severity of AEs. The secondary objectives are:
-Assess the pharmacokinetics by looking at the serum concentration-time
profiles and pharmacokinetic parameters for JNJ-78278343 including but not
limited to Cmax, Tmax, AUC(t1-t2), AUCtau, Cmin, and accumulation ratio (RA)
- Assess the pharmacodynamics by looking at the pharmacodynamic markers
including, but not limited to, systemic cytokine concentrations and serum PSA
- Assess the immunogenicity by looking at the presence of anti-JNJ-78278343
antibodies
- Assess preliminary antitumor activity by looking at the objective response
rate, PSA response, and duration of response according to response criteria of
the Prostate Cancer Working Group 3 (PCWG3).
Study design
This study will be conducted in 2 phases: a Screening Phase (up to 30 days), a
Treatment Phase (start of study drug administration) with an end of treatment
(EOT) visit (up to 30 plus 14 days after last dose of study drug or prior to
the start of a new anticancer therapy), whichever comes first). The total
duration of the study is up to 1 year and 10 months. Safety assessment will
include adverse events (AEs) including dose-limiting toxicity (DLT), serious
adverse events (SAEs), physical examination, vital signs, electrocardiogram,
clinical safety laboratory assessments, Eastern Cooperative Oncology Group
(ECOG) performance status, and neurologic examination.
Intervention
Participants will receive JNJ-78278343 subcutaneously (SC). The dose levels
will be escalated based on the dose limiting toxicities (DLT) evaluation by the
study evaluation team (SET) in Part 1 (dose escalation). In Part 2 (dose
expansion), participants will receive JNJ-78278343 SC at recommended phase 2
dose (RP2D) as determined in Part 1.
Study burden and risks
This is the first clinical study of JNJ-78278343. The potential risks and
mitigation strategies are based on the target expression data, known mechanism
of action (ie, T cell activation and tumor cell lysis), and route of
administration (Table 6 in the protocol).
It is unknown if there is clinical benefit associated with treatment with
JNJ-78278343. JNJ-78278343 has the potential to lead to effective killing of
target cells that express KLK2 such as those in mCRPC and could possibly result
in an increase in progression-free survival (PFS) survival for patients with
advanced disease and limited treatment options.
Antwerpseweg 15-17
Beerse 2340
BE
Antwerpseweg 15-17
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
Each potential participant must satisfy all of the following criteria to be
enrolled in the study:
Age
1. 18 years of age or older.
Disease Characteristics
2. Confirmed adenocarcinoma of the prostate which has spread to other body
parts.
3. Measurable or evaluable disease
4. Prior treatment with at least 1 prior novel androgen receptor (AR)-targeted
therapy or chemotherapy.
5. Prior surgical removal of testicles; or, for participants who have not
undergone surgical removal of testicles, must be receiving ongoing androgen
deprivation therapy (ADT) with a gonadotropin releasing hormone analog.
6. Concurrent use of any other anticancer treatment.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
Any potential participant who meets any of the following criteria will be
excluded from participating in the study:
Disease Conditions
1. Active central nervous system (CNS) involvement.
2. Toxicity related to prior anticancer therapy has not adequately recovered.
Prior/Concomitant Therapy
3. Prior treatment with KLK2-targeted therapy.
4. Received, or are receiving, medications that suppress the immune system
within 3 days prior to the first dose of study drug.
5. Received or plans to receive any live, attenuated vaccine within 4 weeks
prior to the first dose of study drug.
Prior/Concurrent Medical Conditions
6. Diagnosis of cancer other than prostate cancer within 2 years prior to the
first dose of study drug.
7. Solid organ or bone marrow transplantation.
8. Major clotting diseases within one month prior to the first dose of study
drug.
9. Active autoimmune disease within 12 months prior to the first dose of study
drug.
10. Active infection.
11. Major diseases of heart and blood vessels within 6 months prior to the
first dose of study drug.
12. Clinically significant lung diseases.
13. Active or chronic hepatitis B or hepatitis C infection.
14. Known positive test result for human immunodeficiency virus (unless stable
on antiretroviral therapy with undetectable viral load).
16. Any serious underlying medical conditions or other issue that would impair
the ability of the participant to receive or tolerate the planned treatment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506585-31-00 |
| EudraCT | EUCTR2020-005970-83-NL |
| ClinicalTrials.gov | NCT04898634 |
| CCMO | NL76980.031.21 |