A Phase I/II, Single-Arm, Open-Label, Dose-Escalation and Expansion Study of 68Ga-PSMA-0057 and 177Lu-PSMA-0057 in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Chengdu StarRay Therapeutics Co., Ltd
- Enrollment
- 49
- Primary Endpoint
- Incidence of adverse events [68Ga-PSMA-0057]
Overview
Brief Summary
This is a single-arm, open-label, Phase I/II clinical study designed to evaluate the safety, tolerability, pharmacokinetics, dosimetry, pharmacodynamics, and preliminary efficacy of Gallium [68Ga] PSMA-0057 Injection and Lutetium [177Lu] PSMA-0057 Injection as an integrated theranostic regimen in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The study consists of a Phase I dose-escalation phase to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of 177Lu-PSMA-0057, followed by a Phase II dose-expansion phase to further evaluate preliminary antitumor efficacy and confirm safety and pharmacologic profiles. Eligible participants will receive 68Ga-PSMA-0057 for PET imaging and 177Lu-PSMA-0057 for radioligand therapy. Key objectives include characterization of safety, tolerability, pharmacokinetics, dosimetry, pharmacodynamics, and preliminary therapeutic activity.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Able to communicate well with investigators, understand the study purpose and requirements, voluntarily participate, and sign written informed consent.
- •Male, ≥18 years at screening.
- •Histologically or cytologically confirmed prostate cancer (excluding neuroendocrine prostate cancer and small cell prostate cancer), previously treated with at least one novel hormonal agent and 1-2 taxane-based regimens, or deemed intolerant to taxanes.
- •Serum/plasma testosterone at castrate level (\<50 ng/dL or \<1.7 nmol/L).
- •Documented progressive mCRPC based on ≥1 of the following: PSA progression (two consecutive PSA rises ≥1 week apart from a minimum value of 2.0 ng/mL); soft tissue progression per PCWG3 and RECIST v1.1; or bone progression with ≥2 new lesions.
- •PSMA-positive on imaging with 68Ga-PSMA-0057 (within 3 days before treatment start) or other investigator-accepted PSMA tracers (within 6 months before treatment start), using criteria in Section 4.8.
- •At least one measurable lesion per RECIST v1.1 and/or at least one bone metastasis per PCWG
- •Estimated life expectancy ≥12 weeks.
- •ECOG performance status 0-1 at baseline.
- •Adequate organ and bone marrow function, meeting the following lab criteria:
Exclusion Criteria
- •History of hypersensitivity to any study drug component or excipients, or history of specific allergic disease requiring systemic therapy, or other serious allergic reactions.
- •Prior PSMA-targeted radioligand therapy, or treatment with radionuclides such as Sr-89, Sm-153, Re-186, Re-188, Ra-223, or hemibody radiation within 6 months prior to consent.
- •Use of any investigational drug or device within 30 days before consent.
- •Systemic anticancer therapy within 28 days or 5 half-lives prior to consent (whichever is longer), including chemotherapy, radiotherapy, immunotherapy, targeted therapy, systemic immunomodulatory drugs, or antitumor traditional Chinese medicines/formulations within 2 weeks before first dose.
- •Another malignancy within the past 5 years, except for curatively treated cervical carcinoma in situ, non-melanoma skin cancers, etc.
- •Major surgery or significant traumatic injury within 4 weeks before consent.
- •Active brain metastases or CNS involvement, including untreated symptomatic lesions or those requiring radiation, surgery, or steroids within 1 month prior to screening.
- •Symptomatic spinal cord compression or clinical/imaging findings suggestive of impending cord compression.
- •Severe arterial/venous thromboembolic events within 6 months prior to screening; history of stroke; uncontrolled hypertension; decompensated heart failure (NYHA III-IV); LVEF \<50%; unstable angina; clinically significant arrhythmias requiring intervention.
- •Significant acute or chronic infections, including active TB, systemic bacterial or fungal infections requiring systemic therapy.
Arms & Interventions
177Lu-PSMA-0057 Treatment
- Dose Escalation：Enroll patients with PSMA-positive progressive mCRPC who have received at least one novel endocrine therapy and 1-2 taxane-based treatment regimens, or are deemed intolerant by the investigator. Dose escalation will follow the "rolling six design" method, with two planned dose levels: 3.7 GBq and 6.0 GBq of fractionated 177Lu-PSMA-0057, administered every 6 weeks (Q6W), up to a maximum of 6 doses.
- Dose Expansion：After determining the RP2D of 177Lu-PSMA-0057, a phase II expansion will be conducted at the RP2D level (expected to expand only one dose level). Treatment will be administered every 6 weeks (Q6W), up to a maximum of 6 doses.
Intervention: 68Ga-PSMA-0057 (Drug)
177Lu-PSMA-0057 Treatment
- Dose Escalation：Enroll patients with PSMA-positive progressive mCRPC who have received at least one novel endocrine therapy and 1-2 taxane-based treatment regimens, or are deemed intolerant by the investigator. Dose escalation will follow the "rolling six design" method, with two planned dose levels: 3.7 GBq and 6.0 GBq of fractionated 177Lu-PSMA-0057, administered every 6 weeks (Q6W), up to a maximum of 6 doses.
- Dose Expansion：After determining the RP2D of 177Lu-PSMA-0057, a phase II expansion will be conducted at the RP2D level (expected to expand only one dose level). Treatment will be administered every 6 weeks (Q6W), up to a maximum of 6 doses.
Intervention: 177Lu-PSMA-0057 (Drug)
Outcomes
Primary Outcomes
Incidence of adverse events [68Ga-PSMA-0057]
Time Frame: 3 days
Number of participants with adverse events as assessed by NCI-CTCAE v5.0
Incidence of adverse events [177Lu-PSMA-0057]
Time Frame: up to 2 years
Number of participants with adverse events as assessed by NCI-CTCAE v5.0
Incidence of dose limiting toxicities [177Lu-PSMA-0057]
Time Frame: 6 weeks
Number of participants with dose limiting toxicities
Preliminary efficacy: PSA50 response rate (Phase II)
Time Frame: up to 2 years
Proportion of patients achieving ≥50% reduction in prostate-specific antigen (PSA) from baseline.
Secondary Outcomes
No secondary outcomes reported