BELZUTIFAN for Von Hippel-Lindau disease-associated renal cell carcinoma

Inclusion criteria

• {"criterion_text":"- 1. Has the ability to understand and willingness to provide documented informed consent form before the performance of any study-specific procedures\n- 2. 18 years of age or older\n- 3. Has a diagnosis of von Hippel-Lindau disease, based on a germline VHL alteration\n- 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\n- 5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n- 6. Has organ and marrow function as defined in the protocol.\n- 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.\n- 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.\n- 9. Able to swallow oral medications and comply with study procedures"}

Exclusion criteria

• {"criterion_text":"- 1. Has participated in another clinical trial of an investigational drug (or a medical device) within 30 days of study enrollment\n- 10. Has hypersensitivity to the active pharmaceutical ingredient or any component in the Formulation\n- 11. Has an active infection requiring systemic treatment.\n- 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.\n- 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.\n- 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.\n- 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.\n- 16. Adults without legal capacity, under guardianship or curatorship, deprived of their liberty.\n- 2. Has received prior treatment with belzutifan or another HIF-2α inhibitor\n- 3. Has had any systemic anti-cancer therapy (includes anti-VEGF therapy or any systemic investigational anti-cancer agent).\n- 4. Has had radiotherapy within 4 weeks prior to study enrollment.\n- 5. Has had surgical procedure for VHL disease or any major surgical procedure completed within 4 weeks prior to study enrollment.\n- 6. Has an immediate need for surgical intervention for tumor treatment.\n- 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.\n- 8. Evidence of metastatic disease on screening imaging.\n- 9. Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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 Independent Review Committee (IRC)."}

Secondary endpoints

• {"endpoint_text":"- 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.\n- 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.\n- 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.\n- 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.\n- ORR, DOR, TTR, PFS, and TTS for non-RCC tumors associated with VHL disease in individual organ systems.\n- Pharmacokinetics will be evaluated.","definition_or_measurement_approach":"Endpoints are defined in relation to RECIST 1.1 assessments for tumor responses (ORR, DOR, TTR, PFS) and measured as specified (eg, DOR = interval from first documented response to progression or death). Pharmacokinetics will be evaluated per protocol-specified PK assessments."}

Denmark

Latest Decision Or Authorization Date

27-02-2026

Number Of Sites

1

Number Of Participants

9

France

Latest Decision Or Authorization Date

03-03-2026

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Peloton Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Pivotal S.L.

Responsibilities

codes: 1,12,5,7,8

Name

Bioclinica Inc.

Responsibilities

Medical image analysis/ review

Name

MEDPACE LABORATORIES

Responsibilities

code: 4

Name

Medpace Reference Laboratories LLC

Responsibilities

Analysis of blood DNA samples

Third parties

• {"country":"Spain","full_name":"Pivotal S.L.","duties_or_roles":"codes: 1,12,5,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis/ review","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"Analysis of blood DNA samples","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pharma Start LLC","duties_or_roles":"codes: 10,6,7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Canopy Biosciences LLC","duties_or_roles":"RNA testing","organisation_type":"Pharmaceutical company"}