Renal Cell CarcinomaPhase 1NCT03063762
Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6874281 as a Combination Therapy in Participants With Unresectable Advanced and/or Metastatic Renal Cell Carcinoma (RCC)
A Phase 1 study testing Atezolizumab, Bevacizumab and RO6874281 in people with Renal Cell Carcinoma, run by Hoffmann-La Roche at 23 sites in 9 countries.
Trial summary
This is an open-label, multi-center, randomized, Phase 1b, adaptive, clinical study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary therapeutic activity of RO6874281 in combination with atezolizumab with/without bevacizumab in participants with unresectable advanced and/or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Atezolizumab, Bevacizumab and RO6874281
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 23 sitesin 9 countries
- Study dates
- 20 Mar 2017to 14 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unresectable advanced and/or metastatic RCC with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic therapy, including treatment in the adjuvant setting
- During dose escalation only, an additional population with unresectable advanced and/or metastatic 2nd line RCC patients is allowed
- At least one tumor lesion with location accessible to biopsy per clinical judgment of the treating physician
- Consent to provide an archival tumor tissue sample (if available) and to undergo baseline and on treatment tumor biopsies for pharmacodynamic biomarker analysis
- Measurable disease, as defined by RECIST v1.1. At least one lesion accessible for biopsy
- Participants with unilateral pleural effusion are eligible if they fulfill both of the following: (a) New York Heart Association (NYHA) Class 1; (b) Global initiative for obstructive lung disease (GOLD) test level 1 (forced expiratory volume in 1 second [FEV1]/ forced vital capacity [FVC] less than [<] 0.7 and FEV1 greater than or equal to [>=] 80 percent [%] predicted after inhaled bronchodilator)
- Adequate hematological function: neutrophil count of ≥1.5 ≥109 cells/L, platelet count of ≥100,000/≥L, Hb ≥9 g/dL (5.6 mmol/L), lymphocytes ≥0.8 ≥109 cells/L.
Who cannot join
- Symptomatic or untreated central nervous system (CNS) metastases
- Participants with asymptomatic CNS metastases with previous or concomitant brain deficiencies, as defined in the protocol
- Participants with confirmed bilateral pleural effusion
- Episode of significant cardiovascular/cerebrovascular acute disease within 6 months prior to Cycle 1 Day 1
- Active or uncontrolled infections
- Human immunodeficiency virus (HIV) or active Hepatitis A, B, C, D and E virus (HAV, HBV, HCV, HDV and HEV) infection.
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- Major surgery or significant traumatic injury <28 days prior to Cycle 1 Day 1 (excluding fine needle biopsies) or anticipation of the need for major surgery during study treatment
- Serious, non-healing wound; active ulcer; or untreated bone fracture
- Proteinuria as demonstrated by a urine protein to creatinine ratio (UPCR) of >=1.0 at screening
- History of, active or suspicion of autoimmune disease
- Concurrent use of high dose of systemic steroids. The use of inhaled, topical and ophthalmic steroids is allowed.
Trial locations and contacts
23 sites in 9 countries.
23 sites in 9 countries
Spain7 sites
Hospital del Mar; Servicio de Oncologia
Barcelona, 08003
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, 08035
Hospital Clínic i Provincial; Servicio de Oncología
Barcelona, 08036
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, 28034
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
Madrid, 28040
Clinica Universitaria de Navarra; Servicio de Oncologia
Pamplona, Navarre, 31008
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Valencia, 46010
United States3 sites
University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Northwestern Center for Clinical Research; Cancer Center
Chicago, Illinois, 60611
Yale Cancer Center; Medical Oncology
New Haven, Connecticut, 06520
United Kingdom3 sites
Barts & London School of Med; Medical Oncology
London, EC1A 7BE
The Christie
Manchester, M20 4BX
Southampton General Hospital; Medical Oncology
Southampton, SO16 6YD
France2 sites
Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes
Lyon, 69008
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, 31059
Germany2 sites
Universitätsklinikum Tübingen; Klinik für Urologie
Tübingen, 72076
Uniklinikum, Comprehensive Cancer Center Mainfranken; Interdisziplinäres Studienzentrum mit ECTU
Würzburg, 97078
Italy2 sites
Universita di Modena e Reggio Emilia;Dipartimento di Oncologia ed Ematologia
Modena, Emilia-Romagna, 41100
Fondazione IRCCS Policlinico San Matteo, Oncologia
Pavia, Lombardy, 27100
South Korea2 sites
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 135-710
About this study
Official title: An Open-Label, Multi-Center, Randomized, Dose-Escalation, Phase 1b Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6874281 in Combination With Atezolizumab ± Bevacizumab in Patients With Unresectable Advanced and/or Metastatic Renal Cell Carcinoma
This is an open-label, multi-center, randomized, Phase 1b, adaptive, clinical study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary therapeutic activity of RO6874281 in combination with atezolizumab with/without bevacizumab in participants with unresectable advanced and/or metastatic RCC. The study will consist of a dose-escalation part and an extension part.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Atezolizumab, Bevacizumab, RO6874281
- Keywords
- Renal Cell Carcinoma, RO6874281, Atezolizumab, Bevacizumab
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called Tecentriq®
Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.
Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule
BevacizumabDrug
Also called Avastin®
Arms A and B Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) after the atezolizumab administration, and prior to RO6874281 administration as an IV infusion on Days 15, 29, and once in 2 weeks from Day 29 onwards.
In Arm D, Bevacizumab will be administered at a dose of 15mg/kg on Day 8 of Cycle 2 and on Day 8 of each consecutive cycle.
RO6874281Drug
Also called simlukafusp alfa
Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.
In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part
| Study group | Role | What they receive |
|---|---|---|
| Escalation Part (Arm A): Atezolizumab, RO6874281 | Experimental | Participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has complete response (CR), treatment may be discontinued and reintroduced if progressive disease (PD), for a maximum duration of 24 months. Receives: Drug: Atezolizumab; Drug: RO6874281 |
| Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Participants will receive RO6874281 in combination with atezolizumab and bevacizumab until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: RO6874281 |
| Extension Part (Arm A): Atezolizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.
Note: no new participants are being enrolled in the arm at this time. Receives: Drug: Atezolizumab; Drug: RO6874281 |
| Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.
Note: no new participants are being enrolled in the arm at this time. Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: RO6874281 |
| Extension Part (Arm C): Atezolizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.
Note: no new participants are being enrolled in the arm at this time. Receives: Drug: Atezolizumab; Drug: RO6874281 |
| Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.
Note: Arm D is closed for future enrollment Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: RO6874281 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
The first patient in each cohort and regimen will be observed for safety for one week after the administration of RO6874281and atezolizumab +-bevacizumab, prior to enrollment of additional patients in a cohort.
The DLT will be counted for each dose separately and each patient will contribute one single representative data point.
Measured: Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab
Maximum Tolerated Dose (MTD) of RO6874281
The MTD is defined as the highest dose with less than 33% probability of dose limiting toxicity (DLT).
Measured: Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab
Recommended Dose of RO6874281
The recommended dose is defined as the lowest safe dose with the best likelihood for clinical benefit.
Measured: Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab
Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Objective response rate (ORR) defined as the number of patients who achieved an objective response (partial response (PR) plus complete response (CR)) confirmed 28 or more days later, as determined by the Investigator using RECIST v1.1 and modified RECIST criteria at any time during the study divided by the number of response-evaluable patients.
Measured: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Secondary outcomes (18)
Serum RO6874281 Concentration
Pre-infusion, 1 hour (hr) post start of infusion, end of infusion (EOI), 2, 6 hr post EOI on Cycle 1 Day 1; Cycle 1 Days 2, 3; Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 8; Cycle 1 Days 9, 10; Pre-infusion, EOI on Cycle 2 Day 1; Pre-infusion on Cycle 3 Day 1; Cycle 3 Day 2; Pre-infusion on Cycle 4 Day 1; Pre-infusion on Cycle 5 Day 1; Cycle 5 Day 2; Pre-infusion on Day 1; Day 2 in Cycle 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints) (infusion length = 2 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Area Under the Serum Concentration-Time Curve (AUC) for RO6874281
Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 1; Cycle 1 Days 2, 3; Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 8; Cycle 1 Days 9, 10; Pre-infusion, EOI on Cycle 2 Day 1; Pre-infusion on Cycle 3 Day 1; Cycle 3 Day 2; Pre-infusion on Cycle 4 Day 1; Pre-infusion on Cycle 5 Day 1; Cycle 5 Day 2; Pre-infusion on Day 1; Day 2 in Cycle 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints) (infusion length = 2 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Maximum Observed Serum Concentration (Cmax) of RO6874281
Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 1; Cycle 1 Days 2, 3; Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 8; Cycle 1 Days 9, 10; Pre-infusion, EOI on Cycle 2 Day 1; Pre-infusion on Cycle 3 Day 1; Cycle 3 Day 2; Pre-infusion on Cycle 4 Day 1; Pre-infusion on Cycle 5 Day 1; Cycle 5 Day 2; Pre-infusion on Day 1; Day 2 in Cycle 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints) (infusion length = 2 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Serum Atezolizumab Concentration
Pre-infusion, 0.5 hr post EOI on Cycle 1 Day 1; Pre-infusion on Cycle 1 Day 8; Pre-infusion on Day 1 Cycles 2, 3, 4, 5, and 9 onwards; treatment discontinuation; 28, 120 days after last dose (up to 60 months) (Pre-infusion = -4 hr) (infusion length = 1 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
AUC of Atezolizumab
Pre-infusion, 0.5 hr post EOI on Cycle 1 Day 1; Pre-infusion on Cycle 1 Day 8; Pre-infusion on Day 1 Cycles 2, 3, 4, 5, and 9 onwards; treatment discontinuation; 28, 120 days after last dose (up to 60 months) (Pre-infusion = -4 hr) (infusion length = 1 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Cmax of Atezolizumab
Pre-infusion, 0.5 hr post EOI on Cycle 1 Day 1; Pre-infusion on Cycle 1 Day 8; Pre-infusion on Day 1 Cycles 2, 3, 4, 5, and 9 onwards; treatment discontinuation; 28, 120 days after last dose (up to 60 months) (Pre-infusion = -4 hr) (infusion length = 1 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Serum Bevacizumab Concentration
Pre-infusion, 0.5 hr post EOI on Cycle 2 Day 1; Pre-infusion on Cycle 2 Day 8; Pre-infusion on Day 1 Cycles 3, 4, 5, and 9 onwards; treatment discontinuation; 28 days after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 2, 3; -4 hr for other timepoints) (infusion length = 1.5 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
AUC of Bevacizumab
Pre-infusion, 0.5 hr post EOI on Cycle 2 Day 1; Pre-infusion on Cycle 2 Day 8; Pre-infusion on Day 1 Cycles 3, 4, 5, and 9 onwards; treatment discontinuation; 28 days after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 2, 3; -4 hr for other timepoints) (infusion length = 1.5 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Cmax of Bevacizumab
Pre-infusion, 0.5 hr post EOI on Cycle 2 Day 1; Pre-infusion on Cycle 2 Day 8; Pre-infusion on Day 1 Cycles 3, 4, 5, and 9 onwards; treatment discontinuation; 28 days after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 2, 3; -4 hr for other timepoints) (infusion length = 1.5 hr) (1 cycle = 15 days)
Measured: Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Percentage of Participants with Anti-Drug Antibodies (ADA) to RO6874281
Baseline until 3 months post last dose of study treatment (assessed at pre-infusion on Days 1, 8 of Cycle 1; Pre-infusion on Day 1 of Cycles 2, 3, 4, 5, 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose [up to 60 months] [Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints] [infusion length = 2 hr] [1 cycle = 15 days])
Measured: Baseline until 3 months post last dose of study treatment (detailed timeframe is provided in outcome measure description)
Absolute Lymphocytes Count in Peripheral Blood
At baseline; Day 1, 2 3, 8 of Cycle 4. Day 1, 2 of Cycle 5 and Cycle 6. Day 1 of Cycle 7, Cycle 8 and Subsequent Cycles; At treatment discontinuation; 28 days after last dose; 3 months after last dose
Measured: Screening until 120 days post last dose of study treatment (up to 60 months)
Density of Lymphocytes in Tumor Samples
Measured: Archival biopsy: Baseline; Fresh biopsies: Baseline, Day 8 of Cycle 4; Optional biopsies: Any time during the study conduct (1 cycle = 15 days) (up to 60 months)
Percentage of Participants with Programmed Death-Ligand 1 (PD-L1) Status in Tumor Samples
Measured: Archival biopsy: Baseline; Fresh biopsies: Baseline, Day 8 of Cycle 4; Optional biopsies: Any time during the study conduct (1 cycle = 15 days) (up to 60 months)
Percentage of Participants with CR as Determined by the Investigator Using RECIST v1.1
Measured: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Percentage of Participants with Disease Control as Determined by the Investigator Using RECIST v1.1
Measured: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1
Measured: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1
Measured: From randomization until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Overall Survival (OS)
Measured: From randomization until death (up to 60 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2017
- Study start20 Mar 2017
- Primary completion14 Jun 2021
- Study completion14 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03063762
- Sponsor's protocol ID
- BP39365
- Other IDs
- 2016-003528-22, 2016
- Status last verified
- Feb 2023
- First submitted
- 22 Feb 2017
- Last updated
- 17 Feb 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multi-Center, Randomized, Dose-Escalation, Phase 1b Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6874281 in Combination With Atezolizumab ± Bevacizumab in Patients With Unresectable Advanced and/or Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03063762
- Acronym / sponsor ID
- BP39365
- Conditions
- Renal Cell Carcinoma
- Keywords
- Renal Cell Carcinoma, RO6874281, Atezolizumab, Bevacizumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 20 Mar 2017 (actual)
- Primary completion
- 14 Jun 2021 (actual)
- Study completion
- 14 Jun 2021 (actual)
- First posted
- 24 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multi-center, randomized, Phase 1b, adaptive, clinical study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary therapeutic activity of RO6874281 in combination with atezolizumab with/without bevacizumab in participants with unresectable advanced and/or metastatic RCC. The study will consist of a dose-escalation part and an extension part.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Escalation Part (Arm A): Atezolizumab, RO6874281 | Experimental | Drug: Atezolizumab, Drug: RO6874281Participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has complete response (CR), treatment may be discontinued and reintroduced if progressive disease (PD), for a maximum duration of 24 months. |
| Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Drug: Atezolizumab, Drug: Bevacizumab, Drug: RO6874281Participants will receive RO6874281 in combination with atezolizumab and bevacizumab until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. |
| Extension Part (Arm A): Atezolizumab, RO6874281 | Experimental | Drug: Atezolizumab, Drug: RO6874281Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
| Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Drug: Atezolizumab, Drug: Bevacizumab, Drug: RO6874281Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
| Extension Part (Arm C): Atezolizumab, RO6874281 | Experimental | Drug: Atezolizumab, Drug: RO6874281Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
| Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Drug: Atezolizumab, Drug: Bevacizumab, Drug: RO6874281Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: Arm D is closed for future enrollment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Unresectable advanced and/or metastatic RCC with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic therapy, including treatment in the adjuvant setting
- During dose escalation only, an additional population with unresectable advanced and/or metastatic 2nd line RCC patients is allowed
- At least one tumor lesion with location accessible to biopsy per clinical judgment of the treating physician
- Consent to provide an archival tumor tissue sample (if available) and to undergo baseline and on treatment tumor biopsies for pharmacodynamic biomarker analysis
- Measurable disease, as defined by RECIST v1.1. At least one lesion accessible for biopsy
Key exclusion criteria (11 listed)
- Symptomatic or untreated central nervous system (CNS) metastases
- Participants with asymptomatic CNS metastases with previous or concomitant brain deficiencies, as defined in the protocol
- Participants with confirmed bilateral pleural effusion
- Episode of significant cardiovascular/cerebrovascular acute disease within 6 months prior to Cycle 1 Day 1
- Active or uncontrolled infections
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAlso: Tecentriq®Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part. Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule | Drug | Escalation Part (Arm A): Atezolizumab, RO6874281, Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281, Extension Part (Arm A): Atezolizumab, RO6874281, Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281, Extension Part (Arm C): Atezolizumab, RO6874281, Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281 |
| BevacizumabAlso: Avastin®Arms A and B Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) after the atezolizumab administration, and prior to RO6874281 administration as an IV infusion on Days 15, 29, and once in 2 weeks from Day 29 onwards. In Arm D, Bevacizumab will be administered at a dose of 15mg/kg on Day 8 of Cycle 2 and on Day 8 of each consecutive cycle. | Drug | Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281, Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281, Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281 |
| RO6874281Also: simlukafusp alfaArms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part. In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part | Drug | Escalation Part (Arm A): Atezolizumab, RO6874281, Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281, Extension Part (Arm A): Atezolizumab, RO6874281, Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281, Extension Part (Arm C): Atezolizumab, RO6874281, Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281 |
Primary outcome
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time frame: Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab
The first patient in each cohort and regimen will be observed for safety for one week after the administration of RO6874281and atezolizumab +-bevacizumab, prior to enrollment of additional patients in a cohort. The DLT will be counted for each dose separately and each patient will contribute one single representative data point.
Maximum Tolerated Dose (MTD) of RO6874281
Time frame: Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab
The MTD is defined as the highest dose with less than 33% probability of dose limiting toxicity (DLT).
Recommended Dose of RO6874281
Time frame: Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab
The recommended dose is defined as the lowest safe dose with the best likelihood for clinical benefit.
Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Objective response rate (ORR) defined as the number of patients who achieved an objective response (partial response (PR) plus complete response (CR)) confirmed 28 or more days later, as determined by the Investigator using RECIST v1.1 and modified RECIST criteria at any time during the study divided by the number of response-evaluable patients.
18 secondary outcomes
Serum RO6874281 Concentration
Time frame: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Area Under the Serum Concentration-Time Curve (AUC) for RO6874281
Time frame: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Maximum Observed Serum Concentration (Cmax) of RO6874281
Time frame: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Serum Atezolizumab Concentration
Time frame: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
AUC of Atezolizumab
Time frame: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Cmax of Atezolizumab
Time frame: Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Serum Bevacizumab Concentration
Time frame: Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
AUC of Bevacizumab
Time frame: Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Cmax of Bevacizumab
Time frame: Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description)
Percentage of Participants with Anti-Drug Antibodies (ADA) to RO6874281
Time frame: Baseline until 3 months post last dose of study treatment (detailed timeframe is provided in outcome measure description)
Absolute Lymphocytes Count in Peripheral Blood
Time frame: Screening until 120 days post last dose of study treatment (up to 60 months)
Density of Lymphocytes in Tumor Samples
Time frame: Archival biopsy: Baseline; Fresh biopsies: Baseline, Day 8 of Cycle 4; Optional biopsies: Any time during the study conduct (1 cycle = 15 days) (up to 60 months)
Percentage of Participants with Programmed Death-Ligand 1 (PD-L1) Status in Tumor Samples
Time frame: Archival biopsy: Baseline; Fresh biopsies: Baseline, Day 8 of Cycle 4; Optional biopsies: Any time during the study conduct (1 cycle = 15 days) (up to 60 months)
Percentage of Participants with CR as Determined by the Investigator Using RECIST v1.1
Time frame: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Percentage of Participants with Disease Control as Determined by the Investigator Using RECIST v1.1
Time frame: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1
Time frame: Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1
Time frame: From randomization until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months)
Overall Survival (OS)
Time frame: From randomization until death (up to 60 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
23 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atezolizumab, Bevacizumab and RO6874281 in people with Renal Cell Carcinoma, run by Hoffmann-La Roche at 23 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Spain, United States, United Kingdom, France, Germany and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants with Dose-Limiting Toxicities (DLTs) (time frame: Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2023.