177Lu-DOTA-rosopatamab With Best Standard of Care (SoC) for the Second Line of Treatment for Metastatic Castrate-resistant Prostate Cancer, Which Expresses PSMA

Summary

Participation Requirements

Description

This multinational, multicenter, prospective, randomized, controlled, open label Phase 3 study is designed to investigate and confirm the benefits and risks associated with 177Lu DOTA rosopatamab administered together with SoC, as compared to the best SoC alone, in patients with PSMA-positive, metas...

This multinational, multicenter, prospective, randomized, controlled, open label Phase 3 study is designed to investigate and confirm the benefits and risks associated with 177Lu DOTA rosopatamab administered together with SoC, as compared to the best SoC alone, in patients with PSMA-positive, metastatic castration-resistant PC (mCRPC) that has progressed despite prior treatment with a novel androgen axis drug (NAAD). PSMA positivity will be defined by gallium-68 labeled PSMA-11 (68Ga-PSMA-11) positron emission tomography/computerized tomography (PET/CT) as at least one site of metastatic disease with intensity significantly greater than normal liver (i.e., standardized uptake value [SUV] max at least 1.5 times SUV of normal liver. Approximately 387 eligible patients will be randomized to one of two groups in a 2:1 ratio to receive one of the following treatments: Group A: Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best SoC Group B: Best SoC. Randomization of patients to each group will be stratified by the following clinical factors: Prior taxane therapy (yes/no) Prior NAAD in non-metastatic (nm) and/or castration-sensitive (cs) setting (yes/no) Disease burden (defined as: number of bone metastases on 68Ga-PSMA scan < or ? 10). Visceral disease (yes/no) Collection of information on prior and concomitant medications and adverse events (AEs), as well as the review of temporary contra-indications and conditions for withdrawal, will occur at every interaction with the patients. Screening (Day -28 to Day -1, Visit 1) Screening procedures will take place from 28 days (Day -28 to Day -1) prior to enrollment and randomization (on Day 0). Potential participants who provide voluntary written informed consent will undergo Screening evaluations at the clinical site, including a review of the study inclusion/exclusion criteria, full physical examination, safety assessments including safety laboratory investigations (hematology, biochemistry, coagulation, and urinalysis), measurement of vital signs (systolic and diastolic blood pressures, respiratory rate, pulse rate, and body temperature), ECG, imaging (68Ga-PSMA-11 PET/CT scan, Technetium-99m [99mTc] bone scan - if not available from previous records within the last 4 weeks), and CT or MRI (magnetic resonance imaging ) scan (if not available from previous records within the last 4 weeks) as outlined in the Schedule of Assessments. Demographics, height and body weight, medical history, concomitant medication information, performance status assessment using Eastern Cooperative Oncology Group (ECOG), and health-related quality of life (HRQoL) assessment will be undertaken and blood samples for biomarker and CD4/CD8 subset analyses will be collected. Treatment Period (Day 1 [Visit 2] to Day 15 ± 1 [Visit 3]) Patients will return to the clinical site as outpatients on Day 1 (Visit 2) and their eligibility for study participation will be confirmed. Patients meeting all inclusion and no exclusion criteria will be enrolled and randomized. Safety parameters will be assessed, including collection of clinical laboratory samples, measurement of vital signs, ECG, symptom-directed physical examination, collection of ADA samples, and assessment of performance status using ECOG. Patients in Group A will be administered 177Lu-DOTA-rosopatamab on Day 1 (Visit 2). Administration of 177Lu-DOTA-rosopatamab will be performed under the supervision of a nuclear medicine or radiotherapy physician. Patient follow-up and management will be conducted by urologic or oncologic specialists skilled in the management of PC clinical trials. For all patients, the best SoC will be determined by the Principal Investigator (PI). Note: Investigational agents, any form of anti-neoplastic regimens including chemotherapy, platinum based anti-neoplastic drugs, poly adenosine diphosphate ribose polymerase (PARP) inhibitors, other systemic radioisotopes, and hemi-body radiotherapy are excluded from use as best SoC. Use of NAADs, such as abiraterone or enzalutamide, is permitted. Prophylactic use of antihistaminic and/or paracetamol/acetaminophen prior to dosing of the investigational medicinal product (IMP; first and/or second dose) will be allowed at PI(s)'s discretion. All patients will return to the clinical site on Day 15 (Visit 3) for safety monitoring, collection of clinical laboratory samples, collection of samples for urinalysis, collection of samples for biomarker analyses, measurement of vital signs, ECG, symptom-directed physical examination, and assessment of performance status using ECOG. Patients in Group A who do not meet any of the activity reduction criteria (see section below) will also be administered 177Lu-DOTA-rosopatamab on Day 15 (Visit 3). Before administration of the second dose of 177Lu-DOTA-rosopatamab, patients will be assessed and if the hematological toxicity is noted , the patient will undergo a reduction in the administered activity of 177Lu but the rosopatamab total dose will remain at 20mg. Screening (Day -28 to Day -1, Visit 1) Screening procedures will take place from 28 days (Day -28 to Day -1) prior to enrollment and randomization (on Day 0). Potential participants who provide voluntary written informed consent will undergo Screening evaluations at the clinical site, including a review of the study inclusion/exclusion criteria, full physical examination, safety assessments including safety laboratory investigations (hematology, biochemistry, coagulation, and urinalysis), measurement of vital signs (systolic and diastolic blood pressures, respiratory rate, pulse rate, and body temperature), ECG, imaging (68Ga-PSMA-11 PET/CT scan, Technetium-99m [99mTc] bone scan - if not available from previous records within the last 4 weeks), and CT or MRI (magnetic resonance imaging ) scan (if not available from previous records within the last 4 weeks) as outlined in the Schedule of Assessments. Demographics, height and body weight, medical history, concomitant medication information, performance status assessment using Eastern Cooperative Oncology Group (ECOG), and health-related quality of life (HRQoL) assessment will be undertaken and blood samples for biomarker and CD4/CD8 subset analyses will be collected. Treatment Period (Day 1 [Visit 2] to Day 15 ± 1 [Visit 3]) Patients will return to the clinical site as outpatients on Day 1 (Visit 2) and their eligibility for study participation will be confirmed. Patients meeting all inclusion and no exclusion criteria will be enrolled and randomized. Safety parameters will be assessed, including collection of clinical laboratory samples, measurement of vital signs, ECG, symptom-directed physical examination, collection of ADA samples, and assessment of performance status using ECOG. Patients in Group A will be administered 177Lu-DOTA-rosopatamab on Day 1 (Visit 2). Administration of 177Lu-DOTA-rosopatamab will be performed under the supervision of a nuclear medicine or radiotherapy physician. Patient follow-up and management will be conducted by urologic or oncologic specialists skilled in the management of PC clinical trials. For all patients, the best SoC will be determined by the Principal Investigator (PI). Note: Investigational agents, any form of anti-neoplastic regimens including chemotherapy, platinum based anti-neoplastic drugs, poly adenosine diphosphate ribose polymerase (PARP) inhibitors, other systemic radioisotopes, and hemi-body radiotherapy are excluded from use as best SoC. Use of NAADs, such as abiraterone or enzalutamide, is permitted. Prophylactic use of antihistaminic and/or paracetamol/acetaminophen prior to dosing of the investigational medicinal product (IMP; first and/or second dose) will be allowed at PI(s)'s discretion. All patients will return to the clinical site on Day 15 (Visit 3) for safety monitoring, collection of clinical laboratory samples, collection of samples for urinalysis, collection of samples for biomarker analyses, measurement of vital signs, ECG, symptom-directed physical examination, and assessment of performance status using ECOG. Patients in Group A who do not meet any of the activity reduction criteria (see section below) will also be administered 177Lu-DOTA-rosopatamab on Day 15 (Visit 3). Before administration of the second dose of 177Lu-DOTA-rosopatamab, patients will be assessed and if the hematological toxicity is noted as per the below table, the patient will undergo a reduction in the administered activity of 177Lu but the rosopatamab total dose will remain at 20mg. Short-Term Follow-up Visits (Day 22 ± 3 [Visit 4] to Day 113 ± 7 [Visit 9]) All patients will return to the clinical site on Day 22 (Visit 4) for safety monitoring, collection of clinical laboratory samples, collection of samples for urinalysis, measurement of vital signs, symptom-directed physical examination, and assessment of performance status using ECOG. All patients will return to the clinical site on Day 29 (Visit 5) for safety monitoring, collection of clinical laboratory samples, collection of samples for urinalysis, collection of samples for biomarkers and CD4/CD8 subset analysis, measurement of vital signs, symptom-directed physical examination, collection of ADA samples, and assessment of performance status using ECOG and HRQoL. Patients will return to the clinical site on Day 36, 43*, 57, and 113 (Visits 7, 8, 9, and 10) for collection of hematology, biochemistry and coagulation samples, measurement of vital signs, symptom-directed physical examination, and assessment of performance status using ECOG. On Day 57 (Visit 8) and Day 113 (Visit 9) only, assessment of HRQoL and collection of samples for urinalysis will also be conducted. Collection of samples for biomarker and CD4/CD8 subset analysis, 68Ga-PSMA-11 PET/CT and 99mTc bone scans, and CT or MRI scans will occur on Day 57 (Visit 8) only. *Note patients with hematological toxicity will be followed closely until hematological recovery. Complete blood count (CBC) should be collected at least weekly for patients who have not had count recovery by Day 43 until recovery to Grade 2 or higher. Hematology, biochemistry, coagulation and urinalysis testing will only be performed on Day 113 as clinically indicated. Hematology, biochemistry, coagulation and urinalysis testing will only be performed on Day 113 as clinically indicated. Long-Term Follow-up Visits (Day 169 ± 7 [Visit 10] up to 5 years after enrollment in the study) Patients will return to site on Day 169 (Visit 10), Day 253 (Visit 11), Day 337 (Visit 12) and once a year thereafter from time of enrollment (at Years 1, 2, 3, 4, and 5) for collection of samples for biomarker analyses, measurement of vital signs, symptom-directed physical examination, collection of ADA samples (Day 169, Years 1 and 5 only), and assessment of performance status using ECOG and HRQoL, hematology, biochemistry and urinalysis. 99mTc bone scans and CT or MRI scans will also be conducted at all timepoints and 68Ga-PSMA-11 PET/CT will be conducted on Day 169 (Visit 10), Day 253 (Visit 11), and Day 337 (Visit 12).

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