A Multi-Center, Open-Label, Randomized Phase 3 Trial Comparing the Safety and Efficacy of [177Lu]LU-PSMA-I&T versus Hormone Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Curium Pet France

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

20 Feb 2023 → ongoing

Decision date (initial)

2022-12-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CURIUM US LLC

External identifiers

EU CT number

2022-501493-19-00

ClinicalTrials.gov

NCT05204927

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the improvement of radiographic progression-free survival (rPFS) in men with mCRPC treated with [177Lu]LU-PSMA-I&T versus patients treated with hormone therapy

Secondary objectives 9

1. Key Secondary Objective: To evaluate the improvement in overall survival (OS) in men with mCRPC treated with 177Lu-PSMA-I&T compared to hormone therapy.
2. Secondary Objectives: To assess changes in the time to second radiographic progression for patients who crossover from the hormone therapy arm to the [177Lu]LU-PSMA-I&T treatment arm
3. Secondary Objectives: To identify changes in progression-free survival (PFS, composite) following [177Lu]LU-PSMA-I&T radioligand therapy compared to hormone therapy
4. Secondary Objectives: To identify changes in progression-free survival 2 (PFS2, composite) following [177Lu]LU-PSMA-I&T radioligand therapy compared to hormone therapy
5. Secondary Objectives : To assess changes in PSA50 response rate following [177Lu]LU-PSMA-I&T radioligand therapy compared to hormone therapy
6. Secondary Objective : To determine the impact of [177Lu]LU-PSMA-I&T compared to hormone therapy on skeletal symptoms
7. Secondary Objective : To determine the impact of [177Lu]LU-PSMA-I&T compared to hormone therapy on radiographic soft-tissue progression
8. Secondary Objective : To assess changes in use of chemotherapy following [177Lu]LU-PSMA-I&T compared to hormone therapy
9. Secondary Objective : To evaluate the impact on quality of life following [177Lu]LU-PSMA-I&T radioligand therapy compared to hormone therapy

Conditions and MedDRA coding

metastatic Castration-Resistant Prostate Cancer (mCRPC)

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Male 18 years or older able to understand and provide signed written informed consent
2. Life expectancy of at least 6 months as assessed by investigator.
3. Willing to initiate ARAT therapy determined by investigator.
4. For patients who have partners of childbearing potential: The patient and/or partner must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 6 months after the last study drug administration.
5. Histologically or pathologically confirmed prostate adenocarcinoma without predominant small cell component.
6. Progressive disease by one or more of the following criteria: a. Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week apart with a minimum start value of >2 ng/mL. b. Progression of measurable disease (RECIST 1.1) or presence of at least two new bone lesions (PCWG3 criteria).
7. Previous treatment with next-generation androgen receptor (AR)-directed therapy (e.g. abiraterone, enzalutamide, apalutamide, darolutamide). a. Must have received no more than one previous AR-directed therapy. b. Must have been administered ARAT (abiraterone, enzalutamide, darolutamide, or apalutamide) in the castration-sensitive or castrationresistant setting. c. Must have progressed while on ARAT.
8. PSMA-PET scan (e.g. 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by central reader.
9. Effective castration with serum testosterone level of <50 ng/dL and plan to continue with chronic medical or surgical castration
10. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
11. Patients with HIV that are healthy and with a low risk of acquired immune deficiency syndrome related outcomes may participate in the trial at the investigators' discretion.
12. Patients with HBV and HCV may also participate if symptoms are sufficiently managed.
13. ADDITIONAL INCLUSION CRITERIA FOR SUB STUDY: Separate informed consent for participation in the sub-study.
14. ADDITIONAL INCLUSION CRITERIA FOR SUB STUDY: Willing to undergo SPECT: Willing to undergo SPECT/CT imaging at 4 hours, 24 hours, 48 hours, and 7 +/-1 days after 177Lu-PSMA-I&T treatment cycle .
15. ADDITIONAL INCLUSION CRITERIA FOR SUB STUDY: Willing to undergo additional blood sampling for plasma pharmacokinetic measurements.

Exclusion criteria 20

1. Prior treatment with radioligand therapy including other lutetium-labeled compounds.
2. Use of an investigational therapeutic drug within the last 4 weeks prior to start of study treatment or scheduled to receive one during the study period.
3. Known central nervous system (CNS) metastasis unless received therapy, asymptomatic and neurologically stable.
4. Patients receiving zoledronic acid for bone-targeted therapy must be on stable dose for 4 weeks prior to randomization.
5. Major surgery within 30 days of randomization as determined by the Investigator.
6. Patients with active significant cardiac disease defined by any of the following: a. New York Heart Association class 3 or 4 congestive heart failure within 6 months of signing the Informed Consent Form (ICF) unless treated with improvement. b. Current diagnosis of electrocardiogram abnormalities with significant cardiac arrhythmias c. History of long QT syndrome or know history of Torsades de Pointe d. History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months of ICF signature
7. Participants with symptomatic cord compression or clinical/radiological findings indicating impending spinal cord compression
8. Patients with a superscan seen on baseline bone scan as determined by investigator.
9. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer
10. Previous use of G-CSF for persistent neutropenia after standard of care treatment.
11. Participants with active Covid19. Recovered patients may be included when completely recovered (no symptoms at least 28 days before study medication and a negative Covid test within 72 hours).
12. Prior treatment with radium-223 (Xofigo) within the past 12 weeks.
13. Prior chemotherapy treatment for castration-resistant prostate cancer. Prior docetaxel use in the hormone-sensitive setting is permitted as long as no more than 6 doses were received, the last dose was administered >1 year prior to consent and disease progression did not occur during docetaxel treatment.
14. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2
15. Patients with known HRR gene-mutation (BRCA 1/2 encompassing both germline and somatic) who have not been previously treated with olaparib or rucaparib.
16. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
17. Inadequate organ and bone marrow function as evidenced by: a. Hemoglobin < 8 g/dL. b. Absolute neutrophil count < 1.5 x 109/L. c. Platelet count < 100 x 109/L. d. AST/SGOT and/or ALT/SGPT > 3.0 x ULN. e. Total bilirubin > 2 x ULN unless patient has known Gilbert’s syndrome and then may be 3 x ULN. f. Creatinine clearance (CrCl) < 50 mL/min based on the Cockcroft-Gault equation. g. Albumin < 2.75 g/dL
18. Patients who undergo a transfusion for the sole purpose of meeting eligibility for this trial will be excluded.
19. Assessment by the Investigator as unable or unwilling to comply with the requirements of the protocol.
20. ADDITIONAL EXCLUSION CRITERIA FOR SUB STUDY: Unable to undergo SPECT/CT imaging as required in the sub-study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time from randomization to radiographic progression as determined by Prostate Cancer Working Group 3 (PCWG3) criteria as assessed by blinded independent central review

Secondary endpoints 9

1. Time from randomization to death by any cause
2. Time from randomization to the second radiographic progression as determined by PCWG3 or RECIST 1.1 by Blinded Independent Central Review (BICR) after crossover
3. Time from randomization to progression (PFS, composite) based on the following events, whichever occurs first: PCWG3 or RECIST progression, clinical/symptomatic progression and/or pain progression, or death due to any cause as determined by investigator.
4. Time from randomization to the second progression (PFS, composite) based on the following events, whichever occurs first: PCWG3 or RECIST progression, clinical/symptomatic progression and/or pain progression, or death due to any cause as determined by investigator.
5. PSA50 response rate, defined as a confirmed reduction of PSA from baseline of ≥ 50%
6. Time from randomization to first symptomatic skeletal event (SSE-free survival)
7. Time from randomization to radiographic soft tissue progression (rSTP) as measured by RECIST 1.1 by BICR.
8. Time from randomization to first use of chemotherapy
9. Quality of Life improvement based on EORTC QLQ-C30 questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Curium Pet France

Sponsor organisation

Curium Pet France

Address

Biopole Clermont Limagne, 3 Rue Marie Curie 3 Rue Marie Curie

City

St Beauzire

Postcode

63360

Country

France

Scientific contact point

Organisation

Curium Pet France

Contact name

Clinical Development Lead

Public contact point

Organisation

Curium Pet France

Contact name

General Manager

Third parties 1

Sponsor responsibilities

Contact point sponsor

Curium Pet France

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications