Study of DFF332 alone and in combination with Everolimus or Immuno-oncology therapies in patients with renal cell carcinoma and other selected tumors.

Phase 1

• Conditions: Advanced, relapsed Clear Cell Renal Cell Carcinoma; MedDRA version: 21.0Level: LLTClassification code: 10038396Term: Renal carcinoma recurrent Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-513379-41-00
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-02
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

For dose escalation and expansion arms on SA and combos, with the exception of Arm1B: Male and female = 18 years of age, For dose escalation and expansion arms on SA and combos, with the exception of Arm1B: Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC). Disease must be measureable as determined by RECIST v1.1., For dose escalation and expansion arms on SA and combos, with the exception of Arm1B: Patient with unresectable, locally advanced or metastatic ccRCC with documented disease progression following all standard of care therapy, including PD-1/L1 checkpoint inhibitor and a VEGF targeted therapy as monotherapy or in combination. Escalation: No restriction on the number of prior treatments Expansion: Up to 3 prior lines of treatment for advanced/metastatic disease, For dose escalation and expansion arms on SA and combos, with the exception of Arm1B: ECOG performance status = 1, For basket arm (Arm 1B): Male and female of age = 12 years of age., For basket arm (Arm 1B): Histologically confirmed and documented malignancies in the context of the following cancer predisposing syndromes/disorders or harboring somatic mutations on one of these genes: - Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease) - Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma) - Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary paraganglioma and pheochromocytoma syndrome) - Malignancies with EPAS1/HIF2A mutations - Malignancies with ELOC/TCEB1 mutations, For basket arm (Arm 1B): Patients must have either metastatic disease or locally advanced disease that is unresectable or be unfit for resection or other treatment modalities. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, and have no available therapies of proven clinical benefit; or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy., For basket arm (Arm 1B): For patients age = 16 years: ECOG performance status = 1 For patients age = 12 and < 16 years: Lansky performance status = 70

Exclusion Criteria

Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids. Patients with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment prior to study entry and at doses = 10 mg per day prednisone or equivalent for at least 2 weeks before administration of any study treatment., History of seizure disorder and/or extrapyramidal symptoms., Known additional malignancy that is progressing or requires active treatment within the past 3 year(s). Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or other tumors that will not affect life expectancy. Note: for Arm 1B, patients with more than one malignancy are allowed if they are considered to have originated from the same mutation., Patients having out of range lab values during screening and before the first dose of study treatment. Out of range lab values are defined as: - Absolute neutrophil count (ANC) <1.0 × 10e9/L - Platelets <75 × 10e9/L - Hemoglobin (Hgb) < 10g/dL - For adult patients: Serum creatinine > 1.5 × ULN or creatinine clearance < 60mL/min using Cockcroft-Gault formula (Appendix 4) (Cockcroft and Gault 1976). Creatinine clearance may alternatively be measured from a 24-hour urine sample (ClCrm). - For adolescent patients: Calculated creatinine clearance = 70 mL/min/1.73m2 using Schwartz and Work formula (Appendix 4). - Total bilirubin > 1.5 × ULN, except for patients with Gilbert’s syndrome > 3.0 × ULN or direct bilirubin > 1.5 × ULN - Aspartate aminotransferase (AST) > 3 × ULN - Alanine aminotransferase (ALT) > 3 × ULN - Serum electrolytes = grade 2 despite adequate supplementation, Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes: - = 4 weeks for radiation therapy or limited field radiation for palliation within = 2 weeks prior to the first dose of study treatment. - = 4 weeks or = 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent. - = 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin C. - = 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists. - Patients who have undergone major surgery = 4 weeks prior to first dose of study treatment or who have not recovered for the surgical procedure., Patient previously treated with a HIF2a inhibitor.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified