VOLRUSTOMIG for Advanced renal cell carcinoma

Inclusion criteria

• {"criterion_text":"- 1. Age ≥ 18 at the time of screening\n- 2. Body weight > 35 kg\n- 3. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures\n- 4. Histologically or cytologically proven advanced RCC with clear cell component\n- 5. Advanced RCC not previously treated in that setting\n- 6. Provision of tumor material (≥ 5 unstained slides or tissue block) from an archival or fresh tissue biopsy\n- 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n- 8. Subjects must have at least 1 measurable lesion according to RECIST v1.1\n- 9. Life expectancy ≥ 12 weeks\n- 10. Adequate organ and marrow function (in the absence of transfusions or growth factor support within 14 days prior to enrollment) as defined\n- 11. Female subjects of childbearing potential: (a) Must have negative pregnancy test at screening and prior to each administration of investigational product (b) If sexually active with a nonsterilized male partner, must use at least one highly effective method of birth control from screening to 3 months (ie, 90 days; based on 5 half-lives of MEDI5752 + 6 months) after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.\n- 12. Female subjects must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 3 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.\n- 13. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 3 months (90 days) after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib."}

Exclusion criteria

• {"criterion_text":"- 1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results\n- 2. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study\n- 3. Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or any other immune checkpoint inhibitors\n- 4. Previous treatment with VEGF inhibitors\n- 5. Evidence of infections as defined\n- 6. History of organ transplant\n- 7. Active or prior documented autoimmune or inflammatory disorders\n- 8. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of investigational product with listed exceptions to this criterion\n- 9. Poorly controlled blood pressure (BP), defined as BP >= 140/90 mmHg at screening and not able to be controlled prior to Cycle 1 Day 1 and any change in antihypertensive medications within 1 week prior to Cycle 1 Day 1.\n- 10. Thromboembolic (arterial or venous) events within previous 6 months\n- 11. Any concurrent therapy for cancer including, but not limited to, prohibited medications as listed\n- 12. Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product\n- 13. Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression\n- 14. History of another primary malignancy exception\n- 15. Major surgery within 4 weeks prior to enrollment or radiation therapy within 2 weeks prior to enrollment, or has not recovered (ie, ≤- Grade 1 or at baseline) from AEs due to prior treatment\n- 16. Female subjects who are pregnant or breastfeeding as well as male or female subjects of reproductive potential who are not willing to employ one highly effective method of birth control as described\n- 17. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted\n- 18. Uncontrolled intercurrent illness within the last 6 months prior to enrollment including, but not limited to, ongoing or active infection, cardiomyopathy of any etiology, symptomatic congestive heart failure (class > 2 as defined by New York Heart Association), uncontrolled hypertension, unstable angina pectoris, history of myocardial infarction, cardiac arrhythmia, interstitial lung disease, serious chronicgastrointestinal conditions associated with diarrhea\n- 19. Uncontrolled intercurrent illness within the last 6 months prior to enrollment including psychiatric illness/social situations that would limit subject's compliance with study requirements, substantially increase subject's risk of incurring AEs or compromise subject's ability to give informed consent\n- 20. Clinically significant gastrointestinal abnormality including: (a) Malabsorption, gastric resection, or any condition that according to investigator might affect absorption of orally taken medication (b) Active gastrointestinal bleeding in past 3 months (c) History of gastrointestinal perforation or gastrointestinal or non-gastrointestinal fistula in past 3 months\n- 21. Serious nonhealing wound, ulcer, or bone fracture\n- 22. Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of investigational product.\n- 23. Radiographic evidence of major blood vessel invasion/infiltration/encasement"}

Primary endpoints

• {"endpoint_text":"- \"Safety • Incidence of adverse events (AEs)/serious adverse events (SAEs) • Dose-limiting toxicities (DLTs) • AEs leading to discontinuation of treatment • Abnormal laboratory parameters, vital signs, electrocardiogram (ECG) results\"\n- \"Efficacy • Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1\"","definition_or_measurement_approach":"Safety endpoints measured as incidence of AEs/SAEs, DLTs, AEs leading to discontinuation, abnormal labs, vital signs, ECG results. Efficacy measured by Objective Response Rate (ORR) assessed per RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- \"Efficacy • Progression-free survival (PFS), best overall response (BOR), disease control rate (DCR), duration of response (DoR), and time to response (TTR) per RECIST v1.1\"\n- \"Pharmacokinetics • Concentration of MEDI5752 in serum\"\n- \"Immunogenicity • Incidence of antidrug antibodies (ADAs) against MEDI5752 in serum\"","definition_or_measurement_approach":"Efficacy endpoints measured per RECIST v1.1 (PFS, BOR, DCR, DoR, TTR). Pharmacokinetics assessed by serum concentration of MEDI5752. Immunogenicity assessed by incidence of antidrug antibodies (ADAs) in serum."}

France

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

29-10-2025

Processing Time Days

503

Number Of Sites

1

Number Of Participants

9

Spain

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

20-11-2025

Processing Time Days

540

Number Of Sites

11

Number Of Participants

84

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Fortrea Inc.

Responsibilities

Codes: 1;12;2;5;8

Name

Signant Health Global LLC

Responsibilities

Codes: 3

Name

Labcorp Central Laboratory Services SARL

Responsibilities

Laboratory services; Codes: 15 (histopathology); 4

Name

Q Squared Solutions Limited

Responsibilities

Flow cytometry (Code: 15)

Name

Rad Md LLC

Responsibilities

Medical image analysis/review (Code: 15)

Name

Perceptive Informatics Inc.

Responsibilities

Medical image analysis/review (Code: 15)

Name

Cognizant Technology Solutions India Private Limited

Responsibilities

Data/services (Code: 7)

Name

Medable Inc.

Responsibilities

e-diary (Code: 15)

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Codes: 1;12;2;5;8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Codes: 3","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Codes: 15 (value: histopathology); 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Codes: 15 (value: Flow cytometry)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Rad Md LLC","duties_or_roles":"Codes: 15 (value: Medical image analysis/ review - X-ray, MRI, ultrasound, etc.)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Codes: 15 (value: Medical image analysis/ review - X-ray, MRI, ultrasound, etc.)","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Cognizant Technology Solutions India Private Limited","duties_or_roles":"Codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medable Inc.","duties_or_roles":"Codes: 15 (value: e-diary)","organisation_type":"Laboratory/Research/Testing facility"}