An international prospective open-label, multi-center, randomized, non-comparative phase II study of lutetium [177Lu] vipivotide tetraxetan alone and lutetium [177Lu] vipivotide tetraxetan in combination with androgen receptor pathway inhibitors in patients with PSMA PET scan positive castration-resistant prostate cancer (PSMACare)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Feb 2024 → ongoing

Decision date (initial)

2023-12-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2022-503040-41-00

ClinicalTrials.gov

NCT05849298

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate PSA response in participants with CRPC receiving AAA617 alone and participants receiving ARPI and AAA617

Secondary objectives 16

1. To evaluate investigator assessed metastasis-free survival (MFS) in participants receiving AAA617 alone and participants receiving ARPI and AAA617
2. To evaluate Investigator assessed radiographic progression free survival (rPFS) in participants receiving AAA617 alone and participants receiving ARPI and AAA617
3. To evaluate the overall survival (OS) in participants receiving AAA617 alone and participants receiving ARPI and AAA617
4. To evaluate Investigator assessed second progression free survival (PFS2) in participants with CRPC receiving AAA617 alone and in participants receiving ARPI and AAA617
5. To evaluate the time to symptomatic progression in participants receiving AAA617 alone and in participants receiving ARPI and AAA617
6. To evaluate the time to initiation of cytotoxic chemotherapy in participants receiving AAA617 alone and in participants receiving ARPI and AAA617
7. To evaluate the time to first symptomatic skeletal event (SSE) in participants receiving AAA617 alone and participants receiving ARPI and AAA617
8. To evaluate the time to distant metastasis development in participants with CRPC receiving AAA617 and in participants receiving ARPI and AAA617
9. To evaluate the time to local radiological progression in participants with CRPC AAA617 alone and in participants receiving ARPI and AAA617
10. To evaluate time to next therapy or change in therapy in participants receiving AAA617 alone and in participants receiving ARPI and AAA617
11. To evaluate the time to prostate specific antigen (PSA) progression in participants receiving AAA617 alone and in participants receiving ARPI and AAA617
12. To evaluate the time to PSA response in participants with CRPC receiving AAA617 alone and in participants receiving ARPI and AAA617
13. To evaluate the PSA50 response in participants with CRPC receiving AAA617 alone and in participants receiving ARPI and AAA617
14. To evaluate the PSA90 response in participants with CRPC receiving AAA617 alone and in participants receiving ARPI and AAA617
15. To assess the health-related quality of life (HRQoL) in participants receiving AAA617 alone and in participants receiving ARPI and AAA617
16. To evaluate safety and tolerability of AAA617 (CTCAE version 5.0) administered alone and in combination with ARPIs

Conditions and MedDRA coding

PSMA PET scan positive Castration-Resistant Prostate Cancer (CRPC)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002577-PIP01-19, EMEA-002419-PIP02-18

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participants must be adults ≥ 18 years of age with signed informed consent prior to participation to study
2. Histologically or cytologically confirmed prostate cancer
3. Participants must have ongoing androgen deprivation therapy with a GnRH agonist/antagonist or prior bilateral orchiectomy; intermittent androgen deprivation therapy (ADT) before study entry is also permitted if criterion for serum testosterone is met
4. Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl]) on continuous/intermittent GnRH agonist or antagonist therapy or after bilateral orchiectomy
5. Participants must have evidence of PSMA-positive disease (N1 or M1) as seen on a AAA517 or piflufolastat F 18 PET/CT scan at baseline as determined by Blinded Independent Central Review (BICR) based on the methodology proposed in the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) (Eiber et al 2018). Participants with M1 disease on PSMA PET scan are allowed to participate
6. Participants must have a negative conventional imaging for M1 disease.
7. Participants must have adequate organ functions: bone marrow reserve, hepatic & renal

Exclusion criteria 5

1. Prior or present evidence of metastatic disease as assessed locally by CT/MRI for soft tissue disease and whole-body radionuclide bone scan for bone disease. Exception: Participants with pelvic disease may be eligible (e.g., participants with enlarged lymph nodes below the common iliac bifurcation (N1) are eligible per AJCC 8 definition of local disease))
2. Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable with best available standard of care (incl. pads, drainage) are allowed
3. Active clinically significant cardiac disease: history of seizure or condition that may pre-dispose to seizure which may require treatment with surgery or radiation therapy
4. Prior therapy with: second generation anti-androgens (e.g., enzalutamide, apalutamide and darolutamide); CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galeterone, ketoconazole; radiopharmaceutical agents (e.g., Strontium-89), PSMA-targeted radioligand therapy; immunotherapy (e.g., sipuleucel-T); chemotherapy, except if administered in the adjuvant/neoadjuvant setting, completed > 2 years before randomization; any other investigational agents for CRPC; use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethamide) or first-generation anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone) within 28 days before randomization; radiation therapy (external beam radiation therapy [EBRT] and brachytherapy within 28 days before randomization
5. Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, biological therapy or investigational therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PSA response rate is defined as the proportion of participants who have a post-baseline PSA nadir value of ≤0.2ng/mL that is confirmed by a second (the next) PSA measurement ≥4 weeks later.

Secondary endpoints 16

1. MFS is defined as the time from date of randomization to first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., CT/MRI and bone scans) as assessed by investigator using RECIST 1.1 or death due to any cause, whichever occurs first
2. rPFS is defined as the time from the date of randomization to the date of first documented radiographic disease progression by conventional imaging (i.e., CT/MRI and bone scans) as assessed by investigator using RECIST 1.1 or death due to any cause, whichever occurs first
3. OS is defined as the time from the date of randomization to the date of death due to any cause
4. PFS2 defined as time from the date of randomization to the date of first documented disease progression by investigator's assessment (PSA, radiographic, symptomatic, or any combination) on next line of therapy subsequent to MFS event or death due to any cause, whichever occurs first
5. Time to symptomatic progression will be defined as the time from the date of randomization to the date of first documented event for any of the following, whichever occurs first • Development of a symptomatic skeletal event (SSE) • Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy
6. Time to initiation of cytotoxic chemotherapy will be defined as the time from the date of randomization to the date of first documented dose of new cytotoxic chemotherapy being administered to the participant
7. Time to first SSE (TTSSE) defined as the time from the date of randomization to the date of the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death due to any cause, whichever occurs first
8. Time to distant metastasis development is defined as the time from the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., CT/MRI and bone scans) as assessed by investigator using RECIST 1.1
9. Time to local radiological progression is defined as the time from the date of randomization to the date of first documented local radiographic disease progression by conventional imaging (i.e., CT/MRI and bone scans) as assessed by investigator using RECIST 1.1
10. Time to initiation or change in therapy will be defined as the time from the date of randomization to the date of first documented dose of a new / change in therapy being administered to the participant
11. Time from the date of randomization to the date of first documented PSA progression according to PCWG3 guideline criteria. PCWG3 has defined PSA progression as an increase in PSA greater than 25% and >2 ng/ml above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart
12. Calculated as the time from the date of randomization to the date of first documented PSA response with a PSA nadir value of ≤0.2ng/mL
13. PSA50 response is defined as the proportion of participants who have a ≥50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement ≥4 weeks later
14. PSA90 response is defined as the proportion of participants who have a ≥90% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement ≥4 weeks later
15. HRQoL as assessed by Functional Assessment of Cancer Therapy Prostate (FACT-P), Brief Pain Inventory Short From (BPI-SF),) and Functional Assessment of Cancer Therapy (FACT-RNT)
16. Safety: incidence and severity of AEs and serious adverse events (SAEs), changes in laboratory values, vital signs, and ECGs. Any clinically significant lab, vital signs, ECG abnormalities will be captured as an AE. Tolerability: dose interruptions, reductions and dose intensity.

Investigational products

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

Test 7

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 22

Locations

7 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 4 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 78 files

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

Application history

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