Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04626479




Registration number
NCT04626479
Ethics application status
Date submitted
10/11/2020
Date registered
12/11/2020
Date last updated
18/04/2024

Titles & IDs
Public title
Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)
Scientific title
A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC (U03): Substudy 03A
Secondary ID [1] 0 0
MK-3475-03A
Secondary ID [2] 0 0
3475-03A
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Renal Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Other interventions - Favezelimab/Pembrolizumab
Treatment: Drugs - Belzutifan
Treatment: Drugs - Lenvatinib
Other interventions - Pembrolizumab/Quavonlimab
Treatment: Drugs - Vibostolimab/Pembrolizumab

Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib - Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to ~2 years). Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation.

Experimental: Coformulation Favezelimab/Pembrolizumab+ Lenvatinib - Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) PLUS lenvatinib 20 mg. Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.

Experimental: Pembrolizumab + Belzutifan + Lenvatinib - Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~2 years). Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation.

Experimental: Pembrolizumab + Lenvatinib - Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~ 2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.

Experimental: Coformulation Vibostolimab/Pembrolizumab+Belzutifan - Participants will receive vibostolimab/pembrolizumab (coformulation of 200 mg vibostolimab and pembrolizumab 200 mg). Vibostolimab/pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Belzutifan will be administered orally QD until progressive disease or discontinuation.


Other interventions: Pembrolizumab
Administered via IV infusion at a dose of 400 mg Q6W

Other interventions: Favezelimab/Pembrolizumab
Administered via IV infusion at a dose of 800 mg/200 mg Q3W

Treatment: Drugs: Belzutifan
Administered via oral tablet at a dose of 120 mg QD

Treatment: Drugs: Lenvatinib
Administered via oral capsule at a dose of 20 mg QD

Other interventions: Pembrolizumab/Quavonlimab
Administered via IV infusion at a dose of 400 mg/25 mg Q6W

Treatment: Drugs: Vibostolimab/Pembrolizumab
Administered via IV infusion at a dose of 200 mg/200 mg Q6W
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to ~21 days
Primary outcome [2] 0 0
Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)
Timepoint [2] 0 0
Up to ~21 days
Primary outcome [3] 0 0
Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE
Timepoint [3] 0 0
Up to ~21 days
Primary outcome [4] 0 0
Efficacy Phase: Number of participants who experience one or more DLTs
Timepoint [4] 0 0
Up to ~21 days
Primary outcome [5] 0 0
Efficacy Phase: Number of participants who experience one or more AEs
Timepoint [5] 0 0
Up to ~43 months
Primary outcome [6] 0 0
Efficacy Phase: Number of participants who discontinue study treatment due to an AE
Timepoint [6] 0 0
Up to ~43 months
Primary outcome [7] 0 0
Efficacy Phase: Objective response rate (ORR)
Timepoint [7] 0 0
Up to ~43 months
Secondary outcome [1] 0 0
Efficacy Phase: Duration of response (DOR)
Timepoint [1] 0 0
Up to ~43 months
Secondary outcome [2] 0 0
Efficacy Phase: Progression-free survival (PFS)
Timepoint [2] 0 0
Up to ~43 months
Secondary outcome [3] 0 0
Efficacy Phase: Overall survival (OS)
Timepoint [3] 0 0
Up to ~43 months
Secondary outcome [4] 0 0
Efficacy Phase: Clinical benefit rate (CBR)
Timepoint [4] 0 0
Up to ~43 months

Eligibility
Key inclusion criteria
- Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC

- Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant
therapy for RCC is acceptable if completed =12 months before randomization/allocation.

- Is able to swallow oral medication

- Has adequate organ function

- Participants receiving bone resorptive therapy must have therapy initiated at least 2
weeks before randomization/allocation

- Has resolution of toxic effects of the most recent prior therapy to =Grade 1

- Has adequately controlled blood pressure (BP =150/90 mm Hg) with no change in
hypertensive medications within 1 week before randomization/allocation

- Male participants are abstinent from heterosexual intercourse or agree to use
contraception during treatment with and for at least 7 days after the last dose of
lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped,
if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab,
favezelimab/pembrolizumab or a combination of the aforementioned drugs, no
contraception is needed

- Female participants must not be pregnant and not be a woman of childbearing potential
(WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception
during the intervention period and for at least 120 days after the last dose of
pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab for 30 days after
the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from
breastfeeding during the study intervention period and for at least 120 days after
study intervention
Minimum age
18 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has urine protein =1 g/24 hours and has any of the following: (a) a pulse oximeter
reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c)
requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the
first dose of study intervention

- Has clinically significant cardiovascular disease within 12 months from the first dose
of study intervention administration

- Has had major surgery within 3 weeks before first dose of study interventions

- Has a history of lung disease

- Has a history of inflammatory bowel disease

- Has preexisting gastrointestinal (GI) or non-GI fistula

- Has malabsorption due to prior GI surgery or disease

- Has received prior radiotherapy within 2 weeks of start of study intervention

- Has received a live or live attenuated vaccine within 30 days before the first dose of
study drug; killed vaccines are allowed

- Has received more than 4 previous systemic anticancer treatment regimens

- Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive
therapy within 7 days prior to the first dose of study intervention

- Has known additional malignancy that is progressing or has required active treatment
within the past 3 years

- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis

- Has an active autoimmune disease that has required systemic treatment in the past 2
years; replacement therapy is not considered a form of systemic treatment and is
allowed

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of Hepatitis B

- Has had an allogenic tissue/solid organ transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/05/2026
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Western Sydney Local Health District ( Site 1601) - Blacktown
Recruitment hospital [2] 0 0
St George Hospital ( Site 1602) - Kogarah
Recruitment hospital [3] 0 0
Royal Brisbane and Women s Hospital ( Site 1603) - Herston
Recruitment hospital [4] 0 0
Austin Health ( Site 1600) - Heidelberg
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Chile
State/province [12] 0 0
Araucania
Country [13] 0 0
Chile
State/province [13] 0 0
Region M. De Santiago
Country [14] 0 0
Chile
State/province [14] 0 0
Valparaiso
Country [15] 0 0
Colombia
State/province [15] 0 0
Cesar
Country [16] 0 0
Colombia
State/province [16] 0 0
Cordoba
Country [17] 0 0
Colombia
State/province [17] 0 0
Distrito Capital De Bogota
Country [18] 0 0
Colombia
State/province [18] 0 0
Valle Del Cauca
Country [19] 0 0
France
State/province [19] 0 0
Ain
Country [20] 0 0
France
State/province [20] 0 0
Alsace
Country [21] 0 0
France
State/province [21] 0 0
Haute-Garonne
Country [22] 0 0
France
State/province [22] 0 0
Val-de-Marne
Country [23] 0 0
Hungary
State/province [23] 0 0
Pest
Country [24] 0 0
Israel
State/province [24] 0 0
Haifa
Country [25] 0 0
Israel
State/province [25] 0 0
Jerusalem
Country [26] 0 0
Israel
State/province [26] 0 0
Petah Tiqwa
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat Gan
Country [28] 0 0
Israel
State/province [28] 0 0
Tel Aviv
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Seoul
Country [30] 0 0
Netherlands
State/province [30] 0 0
Noord-Holland
Country [31] 0 0
Netherlands
State/province [31] 0 0
Zuid-Holland
Country [32] 0 0
New Zealand
State/province [32] 0 0
Auckland
Country [33] 0 0
Poland
State/province [33] 0 0
Kujawsko-pomorskie
Country [34] 0 0
Poland
State/province [34] 0 0
Mazowieckie
Country [35] 0 0
Poland
State/province [35] 0 0
Pomorskie
Country [36] 0 0
Spain
State/province [36] 0 0
Cataluna
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
United Kingdom
State/province [38] 0 0
England
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Glasgow City
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Lancashire
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Leicestershire
Country [42] 0 0
United Kingdom
State/province [42] 0 0
London, City Of
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Midlothian
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Wales
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Substudy 03A is part of a larger research study that is testing experimental treatments for
renal cell carcinoma (RCC). The larger study is the umbrella study (U03).

The goal of substudy 03A is to evaluate the safety and efficacy of experimental combinations
of investigational agents in participants with advanced first line (1L) clear cell renal cell
carcinoma (ccRCC).

This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety
lead-in phase will be used to demonstrate a tolerable safety profile for the combination of
investigational agents. There will be no hypothesis testing in this study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04626479
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04626479