An Open-Label Phase 2 study to evaluate the effect of PT2977 for the treatment of von Hippel-Lindau Disease-Associated with kidney cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Peloton Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Jan 2019 → ongoing

Decision date (initial)

2024-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Peloton Therapeutics, Inc..

External identifiers

EU CT number

2023-509119-99-00

EudraCT number

2018-000125-30

WHO UTN

U1111-1309-6063

ClinicalTrials.gov

NCT03401788

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Pharmacodynamic, Efficacy

To evaluate the efficacy of PT2977 (belzutifan) for the treatment of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) as measured by overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by an independent review committee (IRC).

Secondary objectives 8

1. To evaluate efficacy of PT2977 (belzutifan) for the treatment of VHL disease-associated RCC measured as follows: Duration of response (DOR), Time to response (TTR), Progression-free survival (PFS), Time to Surgery (TTS)
2. To evaluate efficacy of PT2977 (belzutifan) for the treatment of VHL disease-associated non-RCC tumors (retinal and CNS hemangioblastomas, pancreatic, adrenal, endolymphatic sac tumor and epididymal cystadenomas).
3. To evaluate safety and tolerability of PT2977 (belzutifan)
4. To assess the pharmacokinetics (PK) of PT2977 (belzutifan)
5. Exploratory Objective: To evaluate changes in pharmacodynamic (PD) markers (eg, serum erythropoietin [EPO])
6. Exploratory Objective: To evaluate molecular features associated with predictors of clinical benefit from treatment with belzutifan
7. Exploratory Objective: To evaluate the number of patients who undergo surgical intervention and/or procedures for their RCC and/or non-RCC tumors
8. Exploratory Objective: To evaluate the number of patients who develop metastatic RCC

Conditions and MedDRA coding

Von Hippel-Lindau disease-associated Renal Cell Carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Has the ability to understand and willingness to provide documented informed consent form before the performance of any study-specific procedures
2. 2. 18 years of age or older
3. 3. Has a diagnosis of von Hippel-Lindau disease, based on a germline VHL alteration
4. 4. Has at least 1 measurable solid RCC tumor and no RCC tumor greater than 3.0 cm that requires immediate surgical intervention. The diagnosis of RCC can be radiologic (histologic diagnosis not required). Patients may have VHL disease-associated tumors in other organ systems
5. 5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. 6. Has organ and marrow function as defined in the protocol.
7. 7. Male patients are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of study intervention: A) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent; OR B) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. C) Male patients must also agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex. D) Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
8. 8. A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a WOCBP; OR A) Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a longterm and persistent basis), as described in Appendix 2 during the intervention period and for at least 30 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. B) A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. C) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the patients must be excluded from participation if the serum pregnancy result is positive. D) Additional requirements for pregnancy testing during and after study intervention are located in Appendix 2. E) The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. F) Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. 9. Able to swallow oral medications and comply with study procedures

Exclusion criteria 16

1. 1. Has participated in another clinical trial of an investigational drug (or a medical device) within 30 days of study enrollment
2. 2. Has received prior treatment with belzutifan or another HIF-2α inhibitor
3. 3. Has had any systemic anti-cancer therapy (includes anti-VEGF therapy or any systemic investigational anti-cancer agent).
4. 4. Has had radiotherapy within 4 weeks prior to study enrollment.
5. 5. Has had surgical procedure for VHL disease or any major surgical procedure completed within 4 weeks prior to study enrollment.
6. 6. Has an immediate need for surgical intervention for tumor treatment.
7. 7. Has a prior or concomitant non-VHL disease-associated invasive malignancy with the exception of adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ or any other malignancy from which the patient has remained disease free for more than 2 years.
8. 8. Evidence of metastatic disease on screening imaging.
9. 9. Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease.
10. 10. Has hypersensitivity to the active pharmaceutical ingredient or any component in the Formulation
11. 11. Has an active infection requiring systemic treatment.
12. 12. Has had any major cardiovascular event within 6 months prior to study drug administration including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic event, pulmonary embolism, clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or New York Heart Association Class III or IV heart failure.
13. 13. Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results, in the opinion of the investigator or medical monitor.
14. 14. If a female patient, intends to breast feed a child while on study drug or within 30 days after administration of the last dose of study drug.
15. 15. A WOCBP who has a positive urine pregnancy test within 24 hours prior to the first dose of study intervention (see Appendix 2). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
16. 16. Adults without legal capacity, under guardianship or curatorship, deprived of their liberty.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR) in VHL disease-associated RCC tumors, defined as proportion of patients with a best confirmed response of CR or PR as determined by RECIST 1.1 and as assessed by an IRC.

Secondary endpoints 6

1. Duration of response (DOR) in VHL disease-associated RCC tumors, defined as the interval from the first documentation of response, as determined by RECIST 1.1, to the earlier of the first documentation of disease progression or death from any cause, and calculated for patients with a best confirmed response of CR or PR.
2. Time to response (TTR) in VHL disease-associated RCC tumors, defined as the interval from the start of study treatment to the first documentation of a response, as determined by RECIST 1.1, and calculated for patients with a best confirmed response of CR or PR.
3. Progression-free survival (PFS) in VHL disease-associated RCC tumors, defined as the interval from the start of study treatment until the earlier of the first documentation of disease progression determined by RECIST 1.1 or death from any cause.
4. Time to surgery (TTS) for VHL disease-associated RCC tumors, defined as the interval from the start of study treatment to the date of surgery.
5. ORR, DOR, TTR, PFS, and TTS for non-RCC tumors associated with VHL disease in individual organ systems.
6. Pharmacokinetics will be evaluated.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Peloton Therapeutics Inc.

Sponsor organisation

Peloton Therapeutics Inc.

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Peloton Therapeutics Inc.

Contact name

MK Clinical Director

Public contact point

Organisation

Peloton Therapeutics Inc.

Contact name

MK Clinical Director

Third parties 6

Locations

2 EU/EEA countries · 2 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 16 files

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

Application history

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