Metastatic Castration-resistant Prostate Cancer (mCRPC)
Conditions
Keywords
Metastatic castration-resistant prostate cancer, Immunotherapy, GI-102, CD80-IgG4 Fc-IL2 variant, Interleukin-2, Immunocytokine, bispecific protein, pasritamig, T cell engager
Brief summary
The purpose of this clinical trial is to evaluate the safety, tolerability, and preliminary anti-cancer activity of GI-102 in combination with pasritamig in adult men with metastatic castration-resistant prostate cancer (mCRPC) whose cancer has progressed after previous treatment with a novel hormonal therapy (NHT).
Interventions
DRUGGI-102
GI-102 will be administered via IV infusion
DRUGPasritamig
Pasritamig will be administered via IV infusion.
Sponsors
GI Innovation, Inc.
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are assigned to receive GI-102 in combination with pasritamig sequentially across different dose levels during the Safety run-in phase based on safety and dose-escalation decisions. Participants may subsequently be enrolled in the Expansion phase at the combination recommended Phase 2 dose.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male participants aged ≥18 years (or ≥19 years according to local regulatory requirements). * ECOG performance status of 0 to 1. * Histologically confirmed advanced prostate adenocarcinoma with measurable or evaluable disease. Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted. However, primary small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma (or pathologic evidence of conversion to) is disallowed. * Metastatic castration-resistant prostate cancer (mCRPC) with documented disease progression following at least one line of novel androgen receptor-targeted therapy. * PSA ≥2 ng/mL at screening. * No more than 2 prior taxane regimens and no prior cytotoxic chemotherapy other than taxane therapy. * Prior orchiectomy or ongoing androgen deprivation therapy with castrate testosterone levels. * Adequate organ and marrow function and adequate cardiovascular function. * Adequate recovery from prior anticancer therapy-related adverse events. * Willingness and ability to comply with study procedures and protocol-specified contraception requirements. Key
Exclusion criteria
* Active or prior CNS metastases, carcinomatous meningitis, or clinically unstable spinal cord compression. * Significant uncontrolled cardiovascular, pulmonary, hepatic, autoimmune, infectious, or other systemic disease. * Active or recent clinically significant infection, including active tuberculosis, hepatitis B, or hepatitis C. * Active pneumonitis or interstitial lung disease (ILD), or history of clinically significant pneumonitis/ILD. * Recent treatment with investigational products, prohibited immunomodulating agents, radiotherapy, major surgery, or other protocol-defined prohibited therapies. * Prior treatment with CD3-directed therapies, including KLK2-CD3 bispecific antibodies or other CD3-targeting T-cell engagers. * Known hypersensitivity to GI-102, pasritamig, or their excipients, or any other condition that may interfere with study participation or interpretation of results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and nature of DLTs (Safety run-in phase) | From Day -14 to Cycle 1 Day 22 (35 days) | A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 6.0) or significant laboratory abnormality that occur during the DLT assessment periods, and is considered by the Investigator to be related to the study drug(s). |
| Incidence, nature, and severity of AEs graded according to CTCAE v6.0 (Safety run-in phase) | Up to 2 years | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. |
| PSA response rate (≥ 50% decline from baseline) per PCWG3 (Expansion phase) | Up to 2 years | PSA response rate is defined as the percentage of participants with a decline of PSA of 50% or more from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA response rate (≥ 50% and ≥ 90% decline from baseline) per PCWG3 (Safety run-in phase) | Up to 2 years | PSA response rate is defined as the percentage of participants with a decline of PSA of 50% (or 90%) or more from baseline. |
| Radiographic PFS per PCWG3 | Up to 2 years | Radiographic PFS is defined as the time from the date of first dose of any study treatment until the date of radiographic disease progression or death, whichever comes first. |
| Time to PSA progression | Up to 2 years | Time to PSA progression, defined as the time from baseline to the first date of documented PSA progression per PCWG3 criteria. |
| Overall Response Rate (ORR) per RECIST v1.1 | Up to 2 years | Among participants with measurable disease, ORR is defined as the percentage of participants who achieve a partial response (PR) or complete response (CR) according to RECIST v1.1. |
| Duration of Response (DoR) per RECIST v1.1 | Up to 2 years | Among participants with measurable disease who achieve a CR or PR, DoR is defined as the time from the first documented CR or PR until the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first. |
| Disease Control Rate (DCR) per RECIST v1.1 | Up to 2 years | Among participants with measurable disease, DCR is defined as the percentage of participants who achieve a CR, PR, or stable disease (SD) according to RECIST v1.1. |
| Incidence, nature, and severity of AEs graded according to CTCAE v6.0 (Expansion phase) | Up to 2 years | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. |
| PK profile: peak plasma concentration (Cmax) of GI-102 when combined with pasritamig | Up to 2 years | Plasma concentrations of GI-102 will be measured at specified time points following administration of GI-102 in combination with pasritamig to determine the maximum observed plasma concentration (Cmax). |
| PK profile: half-life (T1/2) of GI-102 when combined with pasritamig | Up to 2 years | Plasma concentrations of GI-102 will be measured at specified time points following administration of GI-102 in combination with pasritamig to determine the terminal half-life (T1/2) of GI-102. |
| PK profile: area under the plasma concentration-time curve (AUC) of GI-102 when combined with pasritamig | Up to 2 years | Plasma concentrations of GI-102 will be measured at specified time points following administration of GI-102 in combination with pasritamig to determine the area under the plasma concentration-time curve (AUC) of GI-102. |
Countries
South Korea, United States
Contacts
CONTACTKwang-Soo Shin
Outcome results
None listed