IMMU-132 in Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Second Generation AR-Directed Therapy
Study Details
Study Description
Brief Summary
This study will investigate the safety and efficacy of IMMU-132 in patients with metastatic castration-resistant prostate cancer progressing on abiraterone or enzalutamide.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This study will investigate the safety and efficacy of IMMU-132 in patients with metastatic castration-resistant prostate cancer progressing on abiraterone or enzalutamide. Patients who have progressed while on therapy with combination enzalutamide/abiraterone or ARN-509/abiraterone as part of ongoing clinical trials are allowed and may be enrolled in the study. To better understand the heterogeneity of response and in particular to identify patients likely to benefit, an extensive correlative biomarker program will be included to collect and analyze tumor tissue biopsies, circulating tumor cells (CTCs), and circulating tumor DNA (ctDNA).
A validated predictive biomarker would benefit the individual patient by enabling him to be treated with a safe effective oral drug and avoid one from which he is unlikely to benefit. It is also essential for prostate cancer drug development because the increasing availability of more life-prolonging therapies is making it more difficult to prove a survival benefit for the next promising agent.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IMMU-132 Treatment Subjects enrolled in this study will receive IMMU-132 as treatment for Castrate-Resistant Prostate Cancer. Dose will be calculated per protocol in milligrams based on the subject's body weight at the beginning of each cycle or more frequently if weight changes >10%. Subjects will be treated on days 1 and 8 in a 21-day cycle, minimum 3 cycles. |
Drug: IMMU-132
IMMU-132 is a novel Antibody Drug Conjugate (ADC) based on a humanized anti-Trop-2 antibody (hRS7) conjugated to SN-38 payload.
Other Names:
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Outcome Measures
Primary Outcome Measures
- PSA response rate [up to 9 weeks]
Subjects who achieve ≥50% PSA decline at or before 9 weeks of therapy with IMMU-132 are considered to have responded. PSA responses will be analyzed by descriptive statistics and summarized in tabular format (frequency tables). The overall PSA response rate will be reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method.
Secondary Outcome Measures
- 6-Month Median Progression Free Survival [6 months]
Proportion of subjects remaining alive and progression free (using PCWG2 criteria) 6 months from time of starting treatment as estimated by the Kaplan-Meier method.
- Median Progression Free Survival Rate [Up to 2 years from start of treatment]
The probability distribution of Progression Free Survival (PFS) will be estimated using the Kaplan-Meier method. The median will be estimated from this distribution. Subjects who have not died or progressed (using PCWG2 criteria) will be censored at the date of last assessment.
- Radiologic Response Rate [up to 2 years from start of treatment]
Number of subjects with reduction in tumor size compared to baseline.
- Median Overall Survival [Up to 2 years from start of treatment]
Overall Survival (OS) is the duration from start of treatment until death from any cause. The probability distribution of OS will be estimated using the Kaplan-Meier method. The median will be estimated from this distribution. Subjects who have not died will be censored at the date of last contact.
- Toxicity rates (Grade 2, Grade 3, Grade 4, Grade ≥ 2, Grade ≥ 3, etc.) [Up to 9 weeks from start of treatment]
Toxicities will be summarized by type and severity in tabular format. Toxicity rates (Grade 2, Grade 3, Grade 4, Grade ≥ 2, Grade ≥ 3, etc.) will be calculated and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Documented histological or cytological evidence of adenocarcinoma of the prostate
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Documented metastatic disease on bone scan and/or CT scans
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Received enzalutamide, abiraterone, or apalutamide. Subjects who have received combination enzalutamide/abiraterone or combination ARN-509/abiraterone as part of ongoing clinical trials are allowed. Subjects who have received TAK-700 (Orteronel®), TOK-001 (Galeterone®), or any other therapeutic investigational product directed towards the AR or androgen biosynthesis are allowed. Prior treatment with first-generation AR antagonists (i.e., bicalutamide, nilutamide, flutamide) before second generation AR-directed therapy is allowed.
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Demonstrated disease progression while on enzalutamide, apalutamide, and/or abiraterone. Progressive disease is defined by one or more of the following:
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A rise in PSA on two successive determinations at least one week apart and PSA level ≥2 ng/mL
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Soft-tissue progression defined by RECIST 1.1
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Bone disease progression defined by PCWG2 with ≥2 new lesions on bone scan
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A minimum serum PSA level of ≥2 ng/mL that is rising based on the PCWG2 criteria
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≥18 y ears of age
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Castrate levels of testosterone (<50 ng/dL [1.74 nmol/L])
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Undergone orchiectomy, or have been on LHRH agonists or antagonists, for at least 3 months prior to study treatment start. Subjects on LHRH agonists/antagonists must remain on these agents for the duration of the study
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ECOG Performance Status of 0-1 (Appendix A)
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Normal organ function with acceptable initial laboratory values within 30 days of study treatment start:
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WBC ≥3000/μl
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ANC ≥1000/μl
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Platelet count ≥100,000/μl
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HGB ≥9 g/dL
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Adequate hepatic function as evidenced by AST/ALT levels <3X the ULN and bilirubin levels of <2.0 mg/dl.
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Adequate renal function as evidenced by serum creatinine of <2.0 mg/dL
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Able to provide written informed consent, or have a legal representative provide written informed consent
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Discontinued enzalutamide, apalutamide, or abiraterone ≥4 weeks prior to study drug initiation
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Subjects must have a previously-acquired biopsy from a metastatic site available
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Subjects must be willing and able (in the opinion of the treating physician) to undergo one research biopsy for the investigational component of this study
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Subjects who have partners of child-bearing potential must be willing to use at least two forms of effective birth control (one form must be a barrier method) during the treatment period and for 90 days after last dose of IMMU-132. Subjects must also agree to not donate sperm through 90 days following the last dose of IMMU-132.
Exclusion Criteria:
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Received prior cytotoxic chemotherapy for CRPC. Prior docetaxel for castration-sensitive disease is permitted.
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Received more than one second generation, FDA approved, AR-directed line of therapy: i.e., sequential enzalutamide-abiraterone or abiraterone-enzalutamide will not be allowed.
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Completed sipuleucel-T (Provenge ®) treatment within 30 days of study treatment start.
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Received any therapeutic investigational agent within 2 weeks of study treatment start.
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Received palliative radiotherapy within 4 weeks of study treatment start.
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Received herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity (e.g., saw palmetto, PC-SPES, PC-HOPE, St. John's wort, selenium supplements, grape seed extract, etc.) within 4 weeks of study treatment start or plans to initiate treatment with these products/alternative therapies during the entire duration of the study.
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Active CNS metastases from prostate cancer. Subjects with treated epidural disease are eligible to enroll. Subjects with treated brain metastases can be included as long as
4 weeks have elapsed since last treatment (radiotherapy or surgery) for brain metastases, the subject is neurologically and radiographically stable, and is not receiving corticosteroids for brain metastases. Subjects with untreated brain metastases are excluded. Brain imaging (CT or MRI) is not required at baseline if brain metastases are not clinically suspected.
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A history within the last 3 years of another invasive malignancy (excluding non-melanoma skin cancer).
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A QTcF interval of >470 msec on the initial Screening ECG; if the Screening ECG QTcF interval is >470 msec, then it may be repeated two more times, and if the mean QTcF of the 3 ECGs is ≤470 msec, the subject may be enrolled.
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A history of clinically significant cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes and second degree or third degree atrioventricular heart block without a permanent pacemaker in place. Subjects with resolved or rate-controlled atrial fibrillation/atrial flutter are allowed.
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NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction/acute coronary syndrome within the preceding 6 months.
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Diabetes mellitus with more than 2 episodes of diabetic ketoacidosis in the 12 months preceding study treatment start.
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Inadequately controlled hypertension (defined as blood pressure >150mmHg systolic and/or >100 mmHg diastolic despite antihypertensive medication) or any history of hypertensive crisis or hypertensive encephalopathy.
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History of loss of consciousness or transient ischemic attack within 12 months before study treatment start.
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Known active HIV, Hepatitis B, or Hepatitis C infections.
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Any other medical, psychiatric, or social condition, including substance abuse, which in the opinion of the Investigator would preclude safe participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
| 2 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 3 | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin | United States | 53792 |
Sponsors and Collaborators
- University of Wisconsin, Madison
- National Cancer Institute (NCI)
- Gilead Sciences
Investigators
- Principal Investigator: Joshua Lang, MD, University of Wisconsin, Madison
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- UW18043
- P30CA014520
- A534260
- SMPH\MEDICINE\HEM-ONC
- NCI-2018-02551
- Protocol Version 12/20/2019