Trial Outcomes & Findings for 177Lu-J591 and 177Lu-PSMA-617 Combination for mCRPC (NCT NCT03545165)

NCT ID: NCT03545165

Last Updated: 2021-08-24

Results Overview

Dose limiting toxicity of combination therapy was determined by monitoring for adverse events following therapy

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: Approximately 3 months after enrollment
• Results posted on: 2021-08-24

Participant Flow

All 6 patients enrolled received both doses.

Participant milestones

Measure	Cohort 1 Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

177Lu-J591 and 177Lu-PSMA-617 Combination for mCRPC

Baseline characteristics by cohort

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Age, Continuous	73 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
Prostate specific antigen (PSA)	94 (ng/mL) n=5 Participants
ECOG score 0	0 Participants n=5 Participants
ECOG score 1	6 Participants n=5 Participants
Halabi (CALGB) score Intermediate	2 Participants n=5 Participants
Halabi (CALGB) score High	4 Participants n=5 Participants
Bone metastases Present	6 Participants n=5 Participants
Bone metastases Absent	0 Participants n=5 Participants
Lymph node metastases Present	4 Participants n=5 Participants
Lymph node metastases Absent	2 Participants n=5 Participants
Visceral metastases Present	3 Participants n=5 Participants
Visceral metastases Absent	3 Participants n=5 Participants
Prior androgen receptor pathway inhibitor Received	6 Participants n=5 Participants
Prior androgen receptor pathway inhibitor Did not receive	0 Participants n=5 Participants
Prior chemotherapy Received	5 Participants n=5 Participants
Prior chemotherapy Did not receive	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 3 months after enrollment

Dose limiting toxicity of combination therapy was determined by monitoring for adverse events following therapy

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Number of Patients With Dose Limiting Toxicity (DLT) of Combination Therapy in a 2-Week Dose-Fractionation Regimen	1 Participants

PRIMARY outcome

Timeframe: Approximately 3 months after enrollment

Cumulative maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of combination therapy was determined by monitoring dose-limiting toxicity and adverse events in the dosing or treatment cohorts

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Cumulative Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D) of Combination Therapy in a 2-Week Dose-Fractionation Regimen	320 mCi

PRIMARY outcome

Timeframe: At baseline and at 2 weeks on therapy

The proportion of patients with PSA decline following treatment with the combination of 177Lu-J591 and 177Lu-PSMA-617 was determined by comparing PSA levels prior to and following radionuclide therapy

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
The Proportion With PSA Decline Following the Dose-Fractionated Combination Therapy by Comparing the Change in PSA Levels After Therapy to the Baseline, Pre-Treatment PSA.	5 Participants

SECONDARY outcome

Timeframe: At the efficacy (scan) visit time point (12 weeks)

Radiographic response rate was determined by scoring follow-up scans after therapy; RECIST 1.1 criteria with PCWG3 modifications were utilized

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Number of Subjects With Radiographic Response by RECIST 1.1 With Prostate Cancer Working Group 3 (PCWG3) Modifications	3 Participants

SECONDARY outcome

Timeframe: Through study completion, up to 26 months

Biochemical progression-free survival was determined from date of first therapy to date of progression by PSA

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Biochemical Progression-Free Survival by PCWG3 Criteria	2.5 months Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: Through study completion, up to 26 months

Radiographic progression-free survival was determined from date of first treatment to date of progression on follow-up imaging

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Radiographic Progression-Free Survival by PCWG3 Criteria	2 months Interval 0.0 to 6.0

SECONDARY outcome

Timeframe: Through study completion, up to 26 months

Overall survival following treatment with the combination of 177Lu-J591 and 177Lu-PSMA-617 was determined from date of first treatment to date of death

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Overall Survival Following Treatment With the Combination of 177Lu-J591 and 177Lu-PSMA-617 in a 2-Week Dose-Fractionation Regimen	8 months Interval 3.0 to 14.0

SECONDARY outcome

Timeframe: At the efficacy (scan) visit time point (12 weeks)

Patients' circulating tumor cell counts were obtained prior to and following therapy

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Changes in CTC Count as Measured by CellSearch Decline	2 Participants
Changes in CTC Count as Measured by CellSearch Increase	4 Participants

SECONDARY outcome

Timeframe: At the efficacy (scan) visit time point (12 weeks)

Patients' circulating tumor cell counts were obtained prior to and following therapy

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Rate of Favorable CTC Count as Measured by Cell Search	0 Participants

SECONDARY outcome

Timeframe: During treatment phase, then every 4 weeks until radiographic progression, assessed up to 6 months

Patient's LDH values were monitored prior to and following therapy

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Rate of Favorable LDH Count	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 weeks

Patients underwent Gallium-68 PSMA PET prior to investigational therapy, and lesions were scored based on SUVmax

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Disease Assessment With PSMA-Ligand Based Imaging Prior to and Following Investigational Treatment Highest lesion SUVmax > 5x liver SUVmean	3 Participants
Disease Assessment With PSMA-Ligand Based Imaging Prior to and Following Investigational Treatment Highest lesion SUVmax 2.5-5x liver SUVmean	2 Participants
Disease Assessment With PSMA-Ligand Based Imaging Prior to and Following Investigational Treatment Highest lesion SUVmax 1-2.5x liver SUVmean	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 weeks

Patients underwent SPECT following administration of radionuclides

Outcome measures

Measure	Cohort 1 n=6 Participants Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Radiation Dosimetry of Combination Therapy Tumor uptake at known sites of disease based on post-treatment planar imaging	6 Participants
Radiation Dosimetry of Combination Therapy No tumor uptake	0 Participants

Adverse Events

Cohort 1

Serious events: 2 serious events

Other events: 6 other events

Deaths: 6 deaths

Serious adverse events

Measure	Cohort 1 n=6 participants at risk Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Metabolism and nutrition disorders dehydration	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Musculoskeletal and connective tissue disorders back pain	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Other adverse events

Measure	Cohort 1 n=6 participants at risk Participants received two doses of 177Lu-J591 (60 mCi) + 177Lu-PSMA-617 (100 mCi), two weeks apart, with minimum 12 weeks of follow-up after last dose.
Gastrointestinal disorders Anorexia	50.0% 3/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Gastrointestinal disorders xerostomia	66.7% 4/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
General disorders fatigue	66.7% 4/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Respiratory, thoracic and mediastinal disorders dyspnea	50.0% 3/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
General disorders transfusion reaction	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Gastrointestinal disorders vomiting	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Gastrointestinal disorders diarrhea	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Renal and urinary disorders hyperkalemia	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Skin and subcutaneous tissue disorders bruising	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Metabolism and nutrition disorders hypocalcemia	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Metabolism and nutrition disorders hypokalemia	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations aspartate aminotransferase increased	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations blood bilirubin increased	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations creatinine increased	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Gastrointestinal disorders nausea	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Renal and urinary disorders hematuria	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations alkaline phosphatase increased	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Musculoskeletal and connective tissue disorders osteonecrosis of jaw	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Musculoskeletal and connective tissue disorders bone pain	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Nervous system disorders peripheral motor neuropathy	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Renal and urinary disorders urinary tract obstruction	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Blood and lymphatic system disorders anemia	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations white blood cell decreased	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations lymphocyte count decreased	50.0% 3/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations neutrophil count decreased	33.3% 2/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Investigations platelet count decreased	16.7% 1/6 • minimum of 30 days following last dose of study drug, up to 26 months Adverse events were assessed and documented at each scheduled study visit and follow-up visit. Serious adverse events include death, life threatening adverse experiences, hospitalization or prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any other serious events that may jeopardize the subject or require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Additional Information

Scott Tagawa MD, Principal Investigator

Weill Cornell Medicine

Phone: 646-962-2072

Email: guonc@med.cornell.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place