Study to Compare Tivozanib in Combination with Nivolumab to Tivozanib Monotherapy in Subjects with Renal Cell Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aveo Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jan 2022 → 20 Jan 2026

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AVEO Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-514570-43-00

EudraCT number

2021-000050-26

ClinicalTrials.gov

NCT04987203

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective of this study is to compare the progression-free survival (PFS) of tivozanib in combination with nivolumab to tivozanib in subjects with renal cell carcinoma (RCC) who have progressed following 1 or 2 lines of therapy which included an immune checkpoint inhibitor (ICI), assessed by a blinded independent radiological review (IRR).

Secondary objectives 4

1. To compare the overall survival (OS) of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib.
2. PFS as assessed by investigator
3. To compare the overall response rate (ORR) and duration of response (DoR) of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib as assessed by blinded IRR and investigator.
4. To assess the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib

Conditions and MedDRA coding

Renal cell carcinoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. ≥ 18 years of age, life expectancy ≥ 3 months.
2. Radiographic disease progression during or following at least 6 weeks of treatment with ICI for locally advanced or metastatic RCC with a clear cell component either in first- or second-line treatment.
3. Subjects must have recovered from the adverse events of prior therapy to grade ≤ 1 or baseline.
4. Histologically or cytologically confirmed RCC with a clear cell component.
5. Measurable disease per RECIST criteria Version 1.1.
6. Eastern Cooperative Oncology Group performance status of 0 or 1.
7. All participants must follow protocol defined contraceptive measures

Exclusion criteria 7

1. Subjects who received: a. A single agent tyrosine kinase inhibitor (TKI) in the first line setting followed by a single agent immune checkpoint inhibitor (ICI) in the second line setting; b. More than 2 prior lines of therapy in the advanced or metastatic setting.
2. History of life-threatening toxicity related to prior immune therapy.
3. Active autoimmune disease as well as those that required discontinuation of prior immuno-oncological (IO) therapy due to immune mediated AEs.
4. Uncontrolled hypertension.
5. More than 1 prior line of therapy with a checkpoint inhibitor in the metastatic setting.
6. Subjects on immune suppressive therapy for organ transplant or subjects with a history of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV) [Patients with HIV who have CD4+ T-cell counts >350 cells/µL, without a history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections, and are on established antiretroviral therapy which does not include a cytochrome P450 (CYP)3A4 inducer, for at least 4 weeks and have an HIV viral load less than 400 copies/mL, are eligible].
7. History of clinically significant interstitial lung disease or current non-infectious pneumonitis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival: Comparison of the PFS of tivozanib in combination with nivolumab to tivozanib in subjects with RCC who have progressed following 1 or 2 lines of therapy. PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to RECIST, or death due to any reasons whichever comes first.

Secondary endpoints 5

1. Overall Survival: Comparison of the OS of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. OS is defined as the time from the date of randomization to date of death due to any cause.
2. Progression free survival: PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to RECIST, or death due to any reasons whichever comes first. PFS as assessed by investigator.
3. Objective Response Rate: Comparison of ORR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. ORR is defined as the proportion of subjects with confirmed complete response or confirmed partial response according to RECIST relative to the total population of randomized subjects.
4. Duration of Response: Comparison of DoR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. DoR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause.
5. Number of subjects with serious and non-serious adverse events: Assessment of the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aveo Pharmaceuticals Inc.

Sponsor organisation

Aveo Pharmaceuticals Inc.

Address

1 Marina Park Drive Floor 12th

City

Boston

Postcode

02210-1832

Country

United States

Scientific contact point

Organisation

Aveo Pharmaceuticals Inc.

Contact name

Chief Medical Officer

Public contact point

Organisation

Aveo Pharmaceuticals Inc.

Contact name

Chief Medical Officer

Third parties 4

Locations

8 EU/EEA countries · 60 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 55 files

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

Application history

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