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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04626518




Registration number
NCT04626518
Ethics application status
Date submitted
10/11/2020
Date registered
12/11/2020
Date last updated
26/01/2024

Titles & IDs
Public title
Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B)
Scientific title
A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC (U03): Substudy 03B
Secondary ID [1] 0 0
MK-3475-03B
Secondary ID [2] 0 0
3475-03B
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 - MK-4830
Treatment: Drugs - Belzutifan
Treatment: Drugs - Lenvatinib
Other interventions - Pembrolizumab/Quavonlimab
Other interventions - Favezelimab/Pembrolizumab

Experimental: Coformulation Pembrolizumab/Quavonlimab - Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg). Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to ~2 years).

Experimental: Coformulation Favezelimab/Pembrolizumab - Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg). Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years).

Experimental: Pembrolizumab + MK-4830 - Participants will receive pembrolizumab 200 mg PLUS MK-4830 800 mg. Both pembrolizumab and MK-4830 will be administered IV Q3W for up to 35 administrations (up to ~2 years).

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

Experimental: Belzutifan + Lenvatinib - Participants will receive Belzutifan 120 mg PLUS lenvatinib 20 mg. 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.


Other interventions: Pembrolizumab
Administered via IV infusion at a dose of 200 mg Q3W or 400 mg Q6W

Other interventions: MK-4830
Administered via IV infusion at a dose of 800 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

Other interventions: Favezelimab/Pembrolizumab
Administered via IV infusion at a dose of 800 mg/200 mg Q3W
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 experienced 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 ~56 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 ~56 months
Primary outcome [7] 0 0
Efficacy Phase: Objective response rate (ORR)
Timepoint [7] 0 0
Up to ~56 months
Secondary outcome [1] 0 0
Efficacy Phase: Duration of response (DOR)
Timepoint [1] 0 0
Up to ~56 months
Secondary outcome [2] 0 0
Efficacy Phase: Progression-free survival (PFS)
Timepoint [2] 0 0
Up to ~56 months
Secondary outcome [3] 0 0
Efficacy Phase: Overall survival (OS)
Timepoint [3] 0 0
Up to ~56 months
Secondary outcome [4] 0 0
Efficacy Phase: Clinical benefit rate (CBR)
Timepoint [4] 0 0
Up to ~56 months

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

- Has experienced disease progression on or after having received systemic. treatment
for locally advanced or metastatic RCC with a PD-(L)1 checkpoint inhibitor (in
sequence or in combination with a vascular endothelial growth factor. - tyrosine
kinase inhibitor [VEGF-TKI]) where PD-(L)1 checkpoint inhibitor treatment progression
is defined by meeting ALL of the following criteria: (a) has received =2 doses of an
anti-PD-(L)1 monoclonal antibody (mAb) (b) has shown radiographic disease progression
during or after an anti-PD-(L)1 mAb as defined by RECIST 1.1 by investigator (c)
disease progression has been documented within 12 weeks from the last dose of an
anti-PD-(L)1 mAb

- Has experienced disease progression on or after having received systemic treatment for
locally advanced or metastatic RCC with a VEGF-TKI (in sequence or in combination with
a PD-[L]1 checkpoint inhibitor) where VEGF-TKI treatment progression is defined by
meeting the following criterion: has shown radiographic disease progression during or
after a treatment with a VEGF-TKI as defined by RECIST 1.1 by investigator.

- 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 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, MK-4830 or a combination of the aforementioned drugs, no
contraception is needed

- Female participant is not pregnant or breastfeeding and is not 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, MK-4830
or 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 previously received treatment with a combination of pembrolizumab plus lenvatinib

- Has received prior treatment with belzutifan

- 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 intervention; 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
17/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
7/09/2025
Actual
Sample size
Target
370
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Western Sydney Local Health District ( Site 3601) - Blacktown
Recruitment hospital [2] 0 0
St George Hospital ( Site 3602) - Kogarah
Recruitment hospital [3] 0 0
Royal Brisbane and Women s Hospital ( Site 3603) - Herston
Recruitment hospital [4] 0 0
Austin Health ( Site 3600) - Melbourne
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 - Melbourne
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
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Chile
State/province [13] 0 0
Araucania
Country [14] 0 0
Chile
State/province [14] 0 0
Region M. De Santiago
Country [15] 0 0
Chile
State/province [15] 0 0
Valparaiso
Country [16] 0 0
France
State/province [16] 0 0
Ain
Country [17] 0 0
France
State/province [17] 0 0
Alsace
Country [18] 0 0
France
State/province [18] 0 0
Haute-Garonne
Country [19] 0 0
France
State/province [19] 0 0
Val-de-Marne
Country [20] 0 0
Hungary
State/province [20] 0 0
Pest
Country [21] 0 0
Israel
State/province [21] 0 0
Haifa
Country [22] 0 0
Israel
State/province [22] 0 0
Jerusalem
Country [23] 0 0
Israel
State/province [23] 0 0
Petah Tiqwa
Country [24] 0 0
Israel
State/province [24] 0 0
Ramat Gan
Country [25] 0 0
Israel
State/province [25] 0 0
Tel Aviv
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Netherlands
State/province [27] 0 0
Noord-Holland
Country [28] 0 0
Netherlands
State/province [28] 0 0
Zuid-Holland
Country [29] 0 0
New Zealand
State/province [29] 0 0
Auckland
Country [30] 0 0
Poland
State/province [30] 0 0
Kujawsko-pomorskie
Country [31] 0 0
Poland
State/province [31] 0 0
Mazowieckie
Country [32] 0 0
Poland
State/province [32] 0 0
Pomorskie
Country [33] 0 0
Spain
State/province [33] 0 0
Cataluna
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
United Kingdom
State/province [35] 0 0
England
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Glasgow City
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Lancashire
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Leicestershire
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London, City Of
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Midlothian
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Wales
Country [42] 0 0
United Kingdom
State/province [42] 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 03B 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 03B is to evaluate the safety and efficacy of experimental combinations
of investigational agents in participants with advanced second line plus (2L+) 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/NCT04626518
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/NCT04626518