177Lu-HTK03170 in mCRPC With PSMA Positive Disease

NCT05570994 | Enrolling By Invitation Phase 1 DMC

• 1 other identifier: H22-02395
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the safe initial injected activity of the radioligand therapy 177Lu-HTK03170 for the measurement of dosimetry and initiation of treatment in subjects with PSMA-positive, metastatic castrate resistant prostate cancer, (mCRPC). Subjects will receive treatment which will be escalated between cycles and personalized based on dosimetry calculations and imaging. In addition, antitumour activity will be measured by radiographic response, and further assessments of the treatment will be measured by CT imaging, ctDNA/ctRNA, PSA, PSMA PET/CT, and quality of life questionnaires. Subjects will be followed for 2 years or until they have progression and are switched to another systemic treatment.

Conditions

Metastatic Castration-resistant Prostate Cancer; Prostate Cancer Metastatic; Castrate Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (6)

• To measure the radiation dosimetry of 177Lu-HTK03170 in subjects who have PSMA-positive mCRPC (confirmed by PSMA PET/CT) previously treated with ARAT

  Phase I: Absorbed doses to organs and tumors per unit of administered activity (Gy/MBq)

  Within 8 weeks of treatments per cycle (cycle durations = 8 weeks)

• To determine the MTIA or a recommended safe initial IA of 177Lu-HTK03170 to measure dosimetry and initiate treatment

  Phase I: Occurrence of dose limiting toxicity (DLT) per protocol

  Within 8 weeks of treatments per cycle (cycle durations = 8 weeks)

• To determine the number of subjects with AEs, Grade 3 or above AEs, drug-related AEs, and SAEs, based on CTCAE v4.03.

  Proportion and distribution of adverse events (AE) is done via the analysis of frequencies for treatment emergent Adverse Event and Serious Adverse Event through the monitoring of relevant clinical and laboratory safety parameters.

  Within 8 weeks of treatments per cycle (cycle durations = 8 weeks)

• To determine the number of subjects with AEs leading to discontinuation

  Proportion of subjects who permanently discontinue 177Lu-HTK03170 due to toxicity or hypersensitivity

  up to 8 weeks post treatment cycle up to 14 weeks post cycle

• Determine the number of subjects with markedly abnormal laboratory tests (including ECG) at least once post-injection

  Analysis of the number of subjects with abnormal labs or ECG data parameters as determined by lab assessment reports and 12-lead electrocardiogram (ECG) reporting

  up to 8 weeks post treatment cycle

• To determine the antitumour effect of 177Lu-HTK03170 therapy measured by radiographic ORR per RECIST v1.1 in subjects who have PSMA-positive mCRPC

  Proportion of subjects achieving a PR, or CR, based on RECIST v1.1

  up to 24 months subsequent follow up evaluations

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  at least 6 months subsequent follow-up evaluations

• Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response

  from date of baseline assessment to at least 4 weeks post treatment cycle Within 8 weeks of treatments per cycle (cycle durations = 8 weeks)

• Duration of PSA responses

  From date of first documented PSA response till 4 weeks follow up, assessed up to 24 months post end of last cycle

• Duration of radiographic response

  From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 24 months from end of last cycle

• Progression free survival at 6 months

  From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 6 months

Other Outcomes (2)

• To assess whether circulating tumour DNA/RNA can be used to predict treatment response

  Baseline (week 0), Cycle 3 (Day 1), Cycle 5 (Day 1) (cycle duration for Cycle 1-5 = 8 weeks

• To assess the dose-response relationship between radiation delivered to tumour lesions and radiographic objective response

  up to 8 weeks following treatment cycle/s (cycle durations = 8 weeks)

Study Arms (1)

177Lu HTK03170 Phase I/II

EXPERIMENTAL

Phase I, the administered activity will be 1.1 GBq ± 10% as an intravenous infusion over a time of 10 to 30 minutes. Initial Activity (IA) escalation will only occur on the initial dosimetry IA, with an increase of 30% over the initial IA (used for dosimetry) at each subsequent level ( 1.65 GBq, 2.5 GBq, 3.7 GBq) in up to 12 participants. Personalized dosimetry will be calculated for each subject. Phase II, subjects will be treated with an initial IA of 177Lu-HTK03170 at the MTIA as determined during Phase I or 13.7 GBq whichever is lower. Treatment is administered as an intravenous infusion over a time of 10 - 30 minutes. Personalized dosimetry will be calculated for each subject so that subsequent treatments will be estimated to remain within the absorbed cumulative dose limits of 28Gy and 35Gy for kidneys and salivary glands, adjusted iteratively over the 4 remaining treatment cycles separated by 8 weeks. Up to 32 subjects will be enrolled to continue efficacy evaluation.

Drug: 177Lu HTK03170; Drug: 68Ga-HTK03149

Interventions

177Lu HTK03170 DRUG

Subjects will receive 177Lu HTK03170 treatment over 5 cycles, each cycle occurs every 8 weeks.

177Lu HTK03170 Phase I/II

68Ga-HTK03149 DRUG

68Ga-HTK03149 PET/CT imaging; intravenous during screening

177Lu HTK03170 Phase I/II

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects ≥ 18 years of age
• Willing and able to provide consent
• Life expectancy of \> 6 months
• Progression on treatment with abiraterone and/or enzalutamide, or similar next generation ARAT therapy, as determined by the investigator. Subjects who have received docetaxel in the castration-resistant setting are also eligible to participate. Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor is permitted.
• Pathologically confirmed prostate adenocarcinoma
• Subjects must have evidence of biochemical or imaging progression. Progression is defined as any one of the following:
• Prostate-specific antigen progression: two consecutive rising PSA values from a baseline measurement with an interval of ≥ 1 week between measurements. Minimum PSA at screening visit is ≥ 2.0 µg/L.
• Soft tissue disease progression on chest, abdomen, pelvis CT or magnetic resonance imaging (MRI; RECIST v1.1)
• Bone progression: ≥ 2 new lesions on bone scan
• Eastern Cooperative Oncology Group (ECOG) performance score ≤2
• Prior orchiectomy, or if on luteinizing hormone releasing hormone (LHRH) agonist/antagonist, then testosterone \< 1.7 nmol/L or \< 50 ng/dL
• Adequate organ function:
• a) Marrow i) Absolute neutrophil count ≥ 1.5 × 109 /L ii) Platelet count ≥ 100 ×109 /L iii) Hemoglobin ≥ 90 g/L with no transfusions in the past 2 weeks b) Kidney i) Estimated creatinine clearance ≥40 ml/min according to Cockroft-Gault equation: ((140 - age) × (weight in kg)) / (72 × (serum creatinine)) c) Liver: i) Bilirubin \< 1.0 × upper limit of normal (ULN) (or if bilirubin is between 1.5 to 2 × ULN, must have a normal conjugated bilirubin) ii) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN in the absence of liver metastases, and) ≤ 5.0 × ULN in the presence of liver metastases.
• Recovery from all previous cancer treatment toxicities to grade ≤ 2 (as per CTCAE 4.03)
• Able to comply with scheduled visits, treatment plans, laboratory tests, imaging tests, and other procedures required and detailed in the protocol.

You may not qualify if:

• Prior treatment with 225Ac-PSMA-617, 177Lu-PSMA, other radiolabeled therapeutic PSMA-ligands, or radio-immunotherapy
• Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or targeted therapy) within 28 days prior to day of enrollment
• Radiotherapy to target lesions (measurable disease) ≤ 4 weeks prior to enrolment
• Known parenchymal brain metastases
• Active epidural disease (treated epidural disease is permitted)
• History of risk factors for xerostomia (ie, head and neck radiation, Sjögren's disease) or pre-existing xerostomia Grade ≥1
• Other concomitant active invasive cancer (except superficial non-melanomatous, non-metastatic skin cancer or non-invasive superficial transitional cell carcinoma \[TCC\])
• Clinically significant cardiac disease including:
• History of unstable angina pectoris, symptomatic pericarditis, or myocardial infarction within 6 months prior to study entry.
• History of documented congestive heart failure (New York Heart Association \[NYHA\] functional classification III-IV) or cardiomyopathy.
• Major surgery within 4 weeks of starting study treatment.
• Unmanageable urinary tract obstruction or hydronephrosis

Sponsors & Collaborators

• British Columbia Cancer Agency: lead

Study Sites (1)

BC Cancer

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective phase I/II study 1-arm study of efficacy and safety of 177Lu HTK03170 for treatment of patients with mCRPC who are referred to BC Cancer - Vancouver for treatment of progressive tumours.

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: October 7, 2022
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)