Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
177Lu-PSMA-617 · 6 trials · 8 indications
rPFS is defined as the time to radiographic progression by Prostate cancer working Group 3 (PCWG3)-modified RECIST v1.1 as assessed by Blinded independent central (BICR) review or death.
ORR is defined as the proportion of participants who experienced complete response (CR) or partial response (PR) during treatment. Tumors will be assessed for response and progression by RECIST version 1.1 by central radiology review.
Treatment emergent adverse events will be classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to Lu-PSMA-617 and liver-directed therapy (if applicable). Descriptive statistics will be utilized to display the data on toxicity seen. Descriptive summaries of discrete data will present the number of study participants and the incidence as a frequency and a percentage.
In GBq, cumulative and average per cycle.
Subacute AESIs are: * treatment-related grade 3-4 thrombopenia persisting more than 12 weeks * treatment-related grade 3-4 neutropenia persisting more than 12 weeks * treatment-related creatinine elevation to \>2x baseline and \>ULN (upper limit of normal) persisting more than 12 weeks * treatment-related grade 4 febrile neutropenia * treatment-related grade 4 non-hematological toxicity
The RP2D will be the highest administered dose level with ≤1 dose-limiting toxicities (DLTs) out of 6 treated patients.
| Arm | Type | Description |
|---|---|---|
| 177Lu-PSMA-617 | EXPERIMENTAL | Participants received 7.4 GBq (200 mCi) +/- 10% 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT could be used. |
| Androgen receptor-directed therapy (ARDT) | ACTIVE_COMPARATOR | For participants randomized to the ARDT arm, abiraterone or enzalutamide was administered per the physician's orders. Best supportive care, including Androgen deprivation therapy (ADT) could be used. |
| Standard of Care | ACTIVE_COMPARATOR | For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order |
| Experimental: 177Lu-PSMA-617 | EXPERIMENTAL | Enrolled participants will complete: * Baseline visit --Imaging every 12 weeks, or 2 cycles * Cycles 1 through 2: * Day 1: Predetermined dose of 177Lu-PSMA-617 1x daily * PSMA PET scan before Cycle 3 Day 1 * Cycles 3 through 6: --Day 1: Predetermined dose of 177Lu-PSMA-617 1x daily * End of treatment visit with assessments * Follow Up: every 6 months for up to 5 years * If no radiographic responses of Complete or Partial Response are seen in the first 9 participants enrolled, the trial will terminate. If 1 or more responses are seen in the first 9 participants, the study will enroll an additional 15 participants. |
| Treatment (177Lu-PSMA-617) | EXPERIMENTAL | Participants with diffusely PSMA-avid disease will receive standard doses of both 177Lu-PSMA-617 (7.4 Gigabequerel (GBq) every 6 weeks for up to 6 cycles) and transarterial chemoembolization (TACE) and/or ablation. Participants with one or more PSMA-negative liver lesions and PSMA-avid disease at all other sites will be treated with a single session of liver-directed therapy (either TACE or ablation) prior to initiation of 177Lu-PSMA-617 treatment. After cycle 2 of 177Lu-PSMA-617, participants who have extrahepatic stable disease/response but hepatic stable disease or progression per RECIST v1.1 will undergo liver-directed therapy. If clinically indicated and extrahepatic disease remains stable after cycle 3 of 177Lu-PSMA-617, participants may undergo a second course of liver-directed therapy. Participants will continue on study until progressive disease, study completion, unacceptable toxicity, or death. |
| Personalized activity | EXPERIMENTAL | - |
| Fixed activity | ACTIVE_COMPARATOR | - |
| Phase 1A: Dose Escalation | EXPERIMENTAL | Participants will be enrolled in a 3+3 dose escalation design to establish a maximum tolerated dose (MTD) of carboplatin, starting at Dose Level 1 and escalating to Dose Level 2 or 3. * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42-day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42-day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone. If 0 out of 3 participants experience a dose-limiting toxicity (DLT), the study will proceed to the next dose level. If 1 or more participants experience a DLT, this dose level is declared the MTD and study will not proceed to expansion. If 1 out of 6 participants at the highest dose level experience DLTs, this is the recommended Phase 1B dose. |
| Phase 1B: Dose Expansion | EXPERIMENTAL | 19 additional participants will be enrolled at the RP2D of carboplatin and will complete: * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Tumor biopsy at baseline and at 12 weeks. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42 day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42 day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone. |
| Name | Type | Description |
|---|---|---|
| 177Lu-PSMA-617 | DRUG | administered intravenously once every 6 weeks (1 cycle) for 6 cycles |
| 68Ga-PSMA-11 | DRUG | single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 185 MBq (3 - 5 mCi). |
| ARDT | DRUG | administered orally on a continuous basis, as per package insert and guidelines |
| ADT | DRUG | ADT are administered as per physician order |
| Ablation | PROCEDURE | Undergo ablation |
| Trans-arterial chemoembolization (TACE) | PROCEDURE | Undergo TACE |
| Positron Emission Tomography (PET)/Computerized tomography (CT) | PROCEDURE | Undergo imaging |
| Tumor Biopsy | PROCEDURE | Undergo biopsy |
| Questionnaire | OTHER | Participant will complete questionnaire |
| Carboplatin | DRUG | Platinum coordination compound, premixed aqueous solution of 10mg/ML, via intravenous (into the vein) infusion per protocol. |
Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. * Participants must be adults \>= 18 years of age. * Participants must have an ECOG performance status of 0 to 1. * Participants must have histological pathological, and/or cytological confirmation o...
177Lu-PSMA-617 is an investigational small molecule being studied for several prostate cancer indications, including metastatic castrate resistant prostate cancer (mCRPC), metastatic hormone sensitive prostate cancer, and metastatic prostate cancer. It is also being evaluated in renal cell carcinoma. The drug is in clinical development and is not yet approved.
177Lu-PSMA-617 targets PSMA, which is an antigen expressed on prostate cancer cells. By binding to PSMA, the drug delivers a radioactive payload (177Lu) directly to the tumor cells. This targeted approach is being studied in multiple clinical trials for prostate cancer and renal cell carcinoma.
177Lu-PSMA-617 is being developed by Novartis AG, which trades under the ticker NVS. The company is conducting several clinical trials of the drug across different prostate cancer settings and in renal cell carcinoma.
177Lu-PSMA-617 is in clinical development across multiple phases. It is being studied in Phase 3 trials for metastatic castrate resistant prostate cancer and metastatic hormone sensitive prostate cancer, a Phase 2 trial for renal cell carcinoma, and a Phase 1 trial for metastatic prostate cancer. It is not FDA approved.
177Lu-PSMA-617 is being evaluated in several trials, including NCT04689828, a Phase 3 study in progressive mCRPC; NCT04720157, a Phase 3 study in metastatic hormone sensitive prostate cancer; NCT06964958, a Phase 2 study in renal cell carcinoma; and NCT07145177, a Phase 1 study combining the drug with liver directed therapy in metastatic prostate cancer.
177Lu-PSMA-617 is the same compound as Pluvicto, which is the brand name used by Novartis. The drug is being studied under the name 177Lu-PSMA-617 in clinical trials for prostate cancer and renal cell carcinoma.