Phase 3 Study of Belzutifan in Combination With Lenvatinib Versus Cabozantinib for Treatment of RCC

JRCT ID: jRCT2031210311

Registered date:13/09/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Renal cell carcinoma
• Date of first enrollment: 18/10/2021
• Target sample size: 35
• Countries of recruitment: Canada,Japan,USA,Japan,Brazil,Japan,France,Japan,Australia,Japan,Germany,Japan,Italy,Japan,The Netherlands,Japan,Belgium,Japan,Spain,Japan,Switzerland,Japan,Finland,Japan,Russia,Japan,UnitedKingdom,Japan,Ireland,Japan,Poland,Japan,Romania,Japan,Austria,Japan,Colombia,Japan
• Study type: Interventional

Intervention(s)

-Belzutifan 120 mg and lenvatinib 20 mg orally once a day
-Cabozantinib 60 mg orally once a day

Outcome(s)

Primary Outcome

-To compare belzutifan+lenvatinib to cabozantinib with respect to PFS per RECIST 1.1 as assessed by blinded independent central review (BICR).
-To compare belzutifan+lenvatinib to cabozantinib with respect to OS.

Secondary Outcome

-To compare belzutifan+lenvatinib to cabozantinib with respect to objective response rate based on RECIST 1.1 as assessed by BICR.
-To evaluate the duration of response as assessed by BICR according to RECIST 1.1.
-To evaluate the safety and tolerability of belzutifan+lenvatinib compared to cabozantinib.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
-Disease progression on or after having received systemic treatment with anti-programmed cell death-1/ligand 1 (PD-1/L1) for locally advanced or metastatic RCC.
-Measurable disease per Response Criteria in Solid Tumors (RECIST) 1.1 criteria as assessed by local study investigator.
-Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
-Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
-Received no more than 2 prior systemic regimens for locally advanced or metastatic RCC.
-Received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastatic RCC.
-A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
-A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
-A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study intervention.
-Adequately controlled blood pressure.
-Adequate organ function.

Exclude criteria

-Is a WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study intervention.
-Hypoxia (pulse oximeter reading <92% at rest), requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
-Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
-Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
-Clinically significant cardiac disease within 6 months of first dose of study intervention.
-Prolongation of QTc interval to >480 ms.
-Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
-Pre-existing >=Grade 3 gastrointestinal or nongastrointestinal fistula.
-Moderate to severe hepatic impairment.
-History of significant bleeding within 3 months before randomization.
-History of solid organ transplantation.
-Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
-Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
-Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
-Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
-Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2 alpha inhibitor.
-Prior treatment with lenvatinib.
-Prior treatment with cabozantinib.
-Currently participating in a study of an investigational agent or using an investigational device.
-Active infection requiring systemic therapy.
-History of human immunodeficiency virus (HIV) infection.
-History of hepatitis B or known active hepatitis C infection.
-History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Related Information

• Primary Sponsor: Iwakami Keiichi
• Secondary ID(s): NCT04586231