Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

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.

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

177Lu HTK03170

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

68Ga-HTK03149

Research Manager

Don Wilson, MD

Maryam Soleimani, MD

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.

Overall, up to 50 subjects will be enrolled to receive an injected activity (IA) of 177Lu-HTK03170. The IA's will be escalated based on personalized dosimetry at subsequent treatments (up to 5 cycles total).

Screening Phase: Subjects will be screened against the inclusion and exclusion criteria. A PSMA PET/CT scan using 68Ga-HTK03149 will be used to confirm PSMA positive disease. Those with confirmed PSMA positive disease with continue to one of the two Treatment Phases. Subjects will be informed which Phase they will be enrolled in.

Subjects will undergo a physical exam, complete a medical history questionnaire, a quality of life questionnaire, blood work, and a diagnostic CT.

Treatment summary per Phase:

The first 3 subjects will receive an initial Initial Acitivity (IA) of 1.1 GBq of 177Lu HTK03170, for the first cycle of treatment, assuming no toxicities occur requiring dose modification. Dosimetry will be performed to obtain absorbed organ dose and effective dose values. The initial IA used for dosimetry will be escalated to improve image quality, radiation dosimetry estimates, and potential efficacy. 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.

IA escalation will cease when a maximum tolerated injected activity (MTIA) is determined or a recommended safe initial IA has been identified based on an integrated assessment of safety, pharmacokinetics (PK), dosimetry, and preliminary antitumour activity data, if available.

Treatment Phase I: During the treatment phase, subjects will undergo up to 5 cycles of treatment. Each treatment cycle will be followed by dosimetry SPECT/CT scans on day 3 (72 +/- 24 hours) after treatment administration, and day 10 (10 days +/- 72 hours) after treatment administration. Additional dosimetry SPECT/CT scans will be completed during Cycle 1, on the day of treatment, and on day 1 (24 hours after treatment). After Cycle 3, a quality of life questionnaire will be completed again.

Treatment Phase II: During the treatment phase, subjects will be treated with an initial IA of 177Lu-HTK03170 at the MTD as determined during Phase I, or 1625 MBq, whichever is lower. Personalized dosimetry will be calculated for each subject as in Phase 1 so that subsequent treatments will be estimated to remain within the absorbed cumulative dose limits of 28Gy and 35Gy for kidneys and salivary glands, respectively, adjusted iteratively over the 3 remaining treatment cycles separated by 8 weeks. Each treatment cycle IA will be further adjusted to ensure a single dose exposure of 2Gy or less to the bone marrow, as needed. Fifteen (15) subjects will be enrolled in the first stage. When 6 or more subjects achieve objective radiographic response based on RECIST v1.1 , the study will proceed to the 2nd stage, where additional 17 subjects will be enrolled to continue efficacy evaluation.

Subjects will undergo up to 5 cycles of treatment. Each treatment cycle will be followed by dosimetry SPECT/CT scans on day 1 (18 - 32 hours after treatment administration) and day 3 (64 - 80h after treatment administration). Additional dosimetry SPECT/CT scans will be completed during Cycle 1, on the day of treatment, and on day 10. A repeat After cycle 5 a quality of life questionnaire will be completed again.

Follow up Phase: At the end of treatment or after discontinuation of any cause, subjects will be followed for 2 years to continue data collection for the other objectives. Objective tumour response will be assessed every 4 months by diagnostic CT according to the RECIST 1.1 criteria. A final quality of life questionnaire will be completed again within 28 days after the last treatment.

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.

177Lu-HTK03170 in mCRPC With PSMA Positive Disease

A Phase I/II Study of 177Lu-HTK03170 in Metastatic, Castration-Resistant Prostate Cancer Subjects With Prostate-specific Membrane Antigen-positive Disease

Proportion of subjects with recurrence as defined by ctDNA/ctRNA allele frequency change from pre-treatment to on-treatment

Proportion of subjects achieving a PR, or CR, based on RECIST v1.1, at different tumour absorbed dose levels

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

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

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.

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

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

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

Proportion of subjects achieving a stable disease lasting for at least 6 months based on RECIST v1.1

Proportion of subjects achieving prostate-specific antigen (PSA) responses defined as a decline of ≥50% decline from baseline

Duration of PSA response was defined as the duration between the date of first document PSA response (i.e. \>= 50% decrease in PSA from Baseline) and the earliest date of PSA progression, where date of PSA progression was defined as: 1) Where a decline from baseline was documented, date that a \>= 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir was documented and confirmed by a second consecutive value obtained at least 4 weeks later.

Duration of radiographic response was defined as the duration between the date of first documented Best Overall Response of Complete Response or Partial Response and the date of first documented radiographic progression or death due to any cause

Proportion of subjects who are progression-free at 6 months as defined by PSA, objective disease, or symptoms. PSA progression, radiographic progression, or clinical progression per PCWG3 criteria will be assessed separately and combined.

Time to PSA progression, radiographic progression, or clinical progression per PCWG3 criteria will be assessed separately and combined.

Time to first Symptomatic Skeletal Event (SSE) was defined as the time (in months) from the date of randomization to the date of the SSE or death from any cause. The SSE date was the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurred first.

The EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ VAS records the patient's self-rated health on a vertical visual analogue 0-100 scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The higher the EQ-VAS score, the better the QoL.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
177Lu-HTK03170 in mCRPC With PSMA Positive Disease	NCT05570994	Metastatic Cast... Prostate Cancer... Castrate Resist...	177Lu HTK03170 68Ga-HTK03149	18 Years -	British Columbia Cancer Agency
177Lu-HTK03170 in mCRPC With PSMA Positive Disease	NCT05570994	Metastatic Cast... Prostate Cancer... Castrate Resist...	177Lu HTK03170 68Ga-HTK03149	18 Years -	British Columbia Cancer Agency

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