A Study to Evaluate Safety and Anti-Tumor Activity of RO7284755 Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
This is an entry-into-human study and will assess the effects of RO7284755 as a single agent and in combination with atezolizumab in adult participants with solid tumors considered responsive to checkpoint inhibition blockade. The maximum duration in the study for each participant will be up to 28 months.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study consists of three parts: dose-escalation of RO7284755 as a single agent (Part 1), dose-escalation of RO7284755 in combination with atezolizumab (Part 2), and extension of RO7284755 as a single agent and/or in combination with atezolizumab (Part 3).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: RO7284755 as a Single Agent Part 1: Dose-escalation of RO7284755 as a single agent. RO7284755 will be either an intravenous administration (IV) or subcutaneous administration (SC) in multiple-ascending doses. |
Drug: RO7284755
Participants will be administered RO7284755 in different schedules.
|
| Experimental: RO7284755 in Combination with Atezolizumab Part 2: Dose-escalation of RO7284755 in combination with atezolizumab. |
Drug: RO7284755
Participants will be administered RO7284755 in different schedules.
Drug: Atezolizumab
Participants will be administered 1200 mg of atezolizumab once every 3 weeks.
Other Names:
|
| Experimental: RO7284755 as a Single Agent and/or with Atezolizumab Part 3: Extension of RO7284755 as a single agent and/or in combination with atezolizumab. |
Drug: RO7284755
Participants will be administered RO7284755 in different schedules.
Drug: Atezolizumab
Participants will be administered 1200 mg of atezolizumab once every 3 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants with Adverse Events in Part 1 and Part 2 [From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)]
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Percentage of Participants with Dose-Limiting Toxicities [From randomization up to day 14 (Part 1) or day 28 (Part 2)]
A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 5) or significant laboratory abnormality that occur during the DLT assessment periods, during Part 1 and Part 2 only, and is considered by the Investigator to be related to RO7284755 or to the combination of RO7284755 and atezolizumab. In Part 2, expected toxicities that are, in the opinion of the Investigator, entirely attributable to atezolizumab, will not be considered DLTs.
- Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Part 3 [From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)]
Objective response rate (ORR) was defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).
- Recommended Dose for Extension (RDE) of RO7284755 in Parts 1 and 2 [From randomization up to day 14 (Part 1) or day 28 (Part 2)]
Secondary Outcome Measures
- Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Parts 1 and 2 [From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)]
ORR was defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).
- Percentage of Participants with Adverse Events in Part 3 [From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)]
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Disease Control Rate in Part 3 [From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)]
The disease control rate was defined as proportion of participants being either responder or in 'stable disease' (SD). To classify a response as SD, measurements will have to be classified as stable (according to RECIST v1.1) at least once at a minimum of 4 weeks after study entry.
- Duration of Response in Part 3 [From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)]
Duration of response will be calculated for 'responder' participants (i.e. best [confirmed] overall response of CR or PR) and will be defined as the time from first occurrence of a documented response until the time of documented disease progression or death (death within 30 days from last study treatment) from any cause, whichever occurs first.
- Progression-free survival (PFS) in Part 3 [From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)]
Progression-free survival was defined as the time from first dose of study treatment to the first occurrence of documented disease progression (based on RECIST 1.1 Investigator's assessment) or death from any cause, whichever occurs first.
- Change from Baseline in Antidrug Antibody (ADA) to RO7284755 [Up to 28 months]
- Percentage of Partcipants with ADAs to RO7284755 [Up to 28 months]
- Area Under the Curve (AUC) for RO7284755 [Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)]
- Minimum Concentration (Cmin) for RO7284755 [Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)]
- Maximum Concentration (Cmax) for RO7284755 [Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)]
- Clearance (CL) for RO7284755 [Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)]
- Volume of Distribution at Steady-State Conditions (Vss) for RO7284755 [Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)]
- Percentage of Immune and Tumor Cells with Positive Programmed Cell Death-1 (PD-1) and Programmed Cell Death-Ligand 1 (PD-L1) Expression in the Tumor Microenvironment (TME) [Baseline]
- Percentage of Immune Cells with CD8+ PD1+ and CD8+ PD1+ TCF7+ Expression [Baseline]
- Blood Tumor Mutational Burden [Baseline]
Blood tumor mutational burden is defined as the number of genetic mutations per megabase (1,000,000 bases).
- Change from Baseline in Percentage of Immune Cell Subsets [Baseline to End of Treatment (up to approximately 28 months)]
Immune cells include NK, CD8, and Treg cells
- Change from Baseline in Percentage of Immune Markers [Baseline to End of Treatment (up to approximately 28 months)]
Immune markers include PD-1, PD-L1, sCD25, cytokines, etc...
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Locally advanced/unresectable or metastatic disease
-
Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
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Eastern Cooperative Oncology Group Performance Status 0 to 1
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Life expectancy of >=12 weeks
-
Consent to provide an archival tumor tissue sample
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Adequate cardiovascular, hematological, coagulative, hepatic and renal function
Exclusion Criteria:
-
Rapid disease progression or suspected hyperprogression or threat to vital organs or critical anatomical sites requiring urgent alternative medical intervention
-
Untreated central nervous system (CNS) metastases
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Treated asymptomatic CNS metastases
-
Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >= 2 weeks before Cycle1 Day 1 (C1D1)
-
Active or history of carcinomatous meningitis/leptomeningeal disease
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Uncontrolled tumor-related pain or symptomatic hypercalcemia
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Concurrent second malignancy
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Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
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Episode of significant cardiovascular/cerebrovascular acute disease within 28 days before study treatment administration
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Active or uncontrolled infections
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Known HIV infection
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Hepatitis B virus (HBV) or hepatitis C virus infection
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Adverse events related to any prior radiotherapy, chemotherapy, targeted therapy, CPI therapy or surgical procedure must have resolved to Grade <=1, except alopecia Grade 2 peripheral neuropathy, and hypothyroidism and/or hypopituitarism on a stable dosage of hormone replacement therapy
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Participants with bilateral pleural effusion
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Major surgery or significant traumatic injury < 28 days before study treatment administration or anticipation of the need for major surgery during study treatment
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Known allergy or hypersensitivity to any component of the formulations of the IMPs to be administered, including but not limited to hypersensitivity to Chinese hamster ovary cell products or other recombinant or humanized antibodies
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History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins
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Previous treatment with Interleukin-2 (IL-2)/Interleukin-5 (IL-15)-like cytokines. IL-2/IL-15 use as an adjunct treatment component for adoptive cell therapy is permitted.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cliniques Universitaires St-Luc | Bruxelles | Belgium | 1200 | |
| 2 | UZ Leuven Gasthuisberg | Leuven | Belgium | 3000 | |
| 3 | Princess Margaret Cancer Center | Toronto | Ontario | Canada | M5G 2M9 |
| 4 | Herlev Hospital; Afdeling for Kræftbehandling | Herlev | Denmark | 2730 | |
| 5 | Rigshospitalet; Fase 1 Enhed - Onkologi | København Ø | Denmark | 2100 | |
| 6 | NKI/AvL | Amsterdam | Netherlands | 1066 CX | |
| 7 | Erasmus MC | Rotterdam | Netherlands | 3015 GD | |
| 8 | Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz | Gdańsk | Poland | 80-214 | |
| 9 | Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz | Warszawa | Poland | 02-781 | |
| 10 | Clinica Universitaria de Navarra; Servicio de Oncologia | Pamplona | Navarra | Spain | 31008 |
| 11 | Hospital del Mar; Servicio de Oncologia | Barcelona | Spain | 08003 | |
| 12 | Vall d´Hebron Institute of Oncology (VHIO), Barcelona | Barcelona | Spain | 08035 | |
| 13 | START Madrid-FJD, Hospital Fundacion Jimenez Diaz | Madrid | Spain | 28040 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BP41628
- 2019-004022-25