IRB Study Number 24-775
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
• To characterize the biodistribution of radiolabeled rosopatamab tetraxetan
• To assess the safety and tolerability of Ac-225 rosopatamab tetraxetan in participants with PSMA PET-positive CRPC who were previously treated with at least one ARSI
• To evaluate efficacy, as defined by biochemical response, in participants who are treated with two dose levels of Ac-225 rosopatamab tetraxetan
Secondary Objectives
• To characterize the biodistribution and pharmacokinetic (PK) profile of rosopatamab tetraxetan and Ac-225 rosopatamab tetraxetan
• To characterize the radiation dosimetry of Ac-225 rosopatamab tetraxetan
• To determine the efficacy of Ac-225 rosopatamab tetraxetan in participants with PSMA PET-positive CRPC who were previously treated with at least one ARSI by comparing biochemical progression-free survival (bPFS) in participants who are treated with two dose levels of Ac-225
Inclusion Criteria
Age
- At least 18 years of age at the time of signing the ICF.
Type of Participant and Disease Characteristics
All Participants
- Progressive CRPC defined as castrate levels of testosterone and progressing by at least one of the following criteria:
a. Serum PSA progression consisting of two consecutive increases in PSA measured at least 1 week apart. The minimal baseline value is 2.0 ng/mL.
b. Soft tissue progression defined as a ≥20% increase in the sum of the diameter (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest sum of the diameter since the previous treatment was started or the appearance of one or more new lesions by CT/magnetic resonance imaging (MRI).
c. Progression of bone disease defined by PCWG3 as evaluable disease or new bone lesions by bone scan.
d. Identification of new soft tissue or bone lesions on PSMA PET imaging.
- Metastatic disease defined as either or both of the following:
a. Parts 1, 2 and 3: Documented M1 disease on conventional imaging (CT/MRI of the chest/abdomen/pelvis and/or Technetium 99m [99mTc] whole-body bone scan)
b. Parts 1 and 2 only: Identification of bone lesion(s), extra-pelvic soft tissue lesion(s), or visceral metastases on PSMA PET imaging with an FDA-approved imaging agent (e.g., 68Ga-PSMA-11, 18F-DCFPyL, or 18F-rhPSMA-7.3)
PSMA PET-positive disease, defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions. PSMA PET-positive lesions are defined as uptake greater than that of liver parenchyma in one or more extra-pelvic metastatic lesions of any size in any organ system using a FDA-approved PSMA PET imaging agent. PSMA PET-negative lesions are defined as PSMA uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any metastatic solid-organ lesion with a short axis of at least 1.0 cm, or in any metastatic bone lesion with a soft tissue component of at least 1.0 cm in the short axis. Participant with any PSMA PET-negative metastatic lesions meeting these criteria are not eligible.
Progression following treatment with ADT and at least one ARSI (e.g., enzalutamide, apalutamide, darolutamide, and/or abiraterone acetate). If a participant is currently on ADT, they should continue ADT for the duration of their participation in the study but will not be permitted to start a new therapy or ADT regimen. If a participant has progressed on an ARSI, they will have the option to remain on the same ARSI or discontinue therapy. If they discontinue the ARSI, a 28-day washout period will be required prior to initiating study intervention.
Prior definitive and palliative external beam radiation therapy and stereotactic body radiation therapy is allowed.
Note: Participants with extended external beam radiation therapy to the axial skeleton, which in the opinion of the Investigator may pose a risk for increased myelotoxicity, will be discussed with the Sponsor to determine eligibility.
- Participants with liver metastases are eligible if they meet the following criteria:
a. ≤3 lesions
b. All lesions must be ≤2 cm in the short axis
c. SUVmean ≥2 x that of liver parenchyma
Part 3 Participants
Prior treatment with Lu-177-PSMA-RL, defined as up to six doses of Lu-177-PSMA-617 (i.e., Pluvicto) or investigational use of up to four doses of Lu-177-PSMA-I&T.
Prior treatment with one taxane-based chemotherapy is allowed, but not required. A taxane-based chemotherapy is defined as a minimum exposure of two cycles of a taxane chemotherapy.
Diagnostic Assessments
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Demonstrate adequate organ function as defined below. All screening laboratories should be performed within 10 days of initiating study intervention.
Sex and Reproduction
- For participants who have partners of childbearing potential:
Participants and/or female partners must use a highly effective method of birth control along with adequate barrier protection deemed acceptable by the Investigator or abstain from intercourse during the study and for 5 months after the last dose administration. Male participants must agree not to donate sperm during this time.
Informed Consent
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Exclusion Criteria
Medical Conditions
Superscans by nuclear medicine/99mTc bone scan.
A known malignancy that is progressing or has required active treatment within the past 3 years other than CRPC, which is expected to alter life expectancy or may interfere with CRPC disease assessment. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or progressive carcinomatous meningitis, or progressive leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. For participants with CNS metastases to be eligible, they must have completed radiotherapy at least 14 days prior to enrollment and require N-methyltyramine 4 mg of dexamethasone or equivalent steroid medication for at least 4 weeks and are clinically stable with no evidence of progression at time of study enrollment. If anticonvulsant medication is required, participant must be stable for minimally 28 days on an anticonvulsant regimen.
Untreated moderate to severe hydronephrosis. If hydronephrosis is corrected via stent or nephrostomy, hydronephrosis will be considered resolved.
Any evidence of hepatic fibrosis.
A known active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Active viral (any etiology) hepatitis participants are excluded. Participants with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen test and a positive anti‑hepatitis core antigen antibody test) who have a viral load below the limit quantification (HBV DNA titer < 1000 cps/mL or 200 IU/mL) and are not currently on viral suppressive therapy may be eligible and should be discussed with the Sponsor’s Medical Monitor (or designee). Note, participants with a history of hepatitis C virus (HCV) infection should have completed curative antiviral treatment and have a viral load below the limit of quantification to be eligible to enroll into the study. Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority
Uncontrolled diabetes. Participants with controlled diabetes are allowed (insulin is allowed).
Uncontrolled hypertension, defined as blood pressure 160/100 mm Hg despite antihypertensive medication.
History of myocardial infarction or arterial thromboembolic events within 6 months prior to enrollment or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 470 msec.
An active infection requiring systemic therapy.
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participants’ participation for the full duration of the study, or is not in the best interest of the participants to participate, in the opinion of the treating Investigator.
History of known platelet malfunction and/or disorder, including but not limited to idiopathic immune thrombocytopenia and thrombotic thrombocytopenia purpura.
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
Active autoimmune disease that has required systemic treatment within 90 days (i.e., with the use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid [stable / low doses of ≤10 mg/day prednisone or equivalent dose]) for adrenal or pituitary insufficiency is not considered a form of systemic treatment and is allowed.
Prior Therapy
All Participants
Prior platinum-based chemotherapy.
Prior PARP inhibitors (e.g., olaparib or rucaparib).
Extended external beam radiation therapy to the axial skeleton, which in the opinion of the Investigator may pose a risk for increased myelotoxicity. These participants should be discussed with the Sponsor to determine eligibility.
Any systemic anticancer therapy (e.g., chemotherapy, immunotherapy, or biological therapy [including monoclonal antibodies]) or any investigational agents, aside from ARSI or ADT (see Inclusion Criterion #5), within 28 days prior to randomization.
Have received a live virus vaccination within 28 days of the first dose of study intervention. Seasonal flu vaccines that do not contain live virus are permitted.
Part 2 Participants
Prior chemotherapy for CRPC. Prior taxane chemotherapy for HSPC is allowed if discontinued ≥1 year prior to randomization.
Prior radiopharmaceutical therapy (e.g., Ra-223, Lu-177-PSMA-617, or Lu-177-PSMA-I&T).
Prior PSMA-targeted therapy (e.g., radioligand therapy, antibody-drug conjugates, or CAR-T therapy).
Part 3 Participants
- Prior PSMA-targeted therapy (e.g., antibody-drug conjugates or CAR-T therapy), except for Lu-177-PSMA-RL therapy.
Prior/Concurrent Clinical Study Experience
Participants receiving anti-coagulants or anti-platelet drugs (e.g., aspirin or nonsteroidal anti-inflammatory drugs [NSAIDs]) who cannot discontinue use if platelet count decreases to <50,000.
Are currently participating in or have participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study intervention. Note: Participation in an observational study is an exception to this criterion and may qualify for the study with Sponsor approval Note: Participants who have entered the follow-up of an investigational study may participate as long as it has been 28 days after the last dose of the previous investigational agent
