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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

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04303858
Recruitment Status : Recruiting
First Posted : March 11, 2020
Last Update Posted : June 5, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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
Solid Tumors Drug: RO7284755 Drug: Atezolizumab 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Randomized, Dose-Escalation and Extension, Phase IA/IB Study to Evaluate Safety and Anti-Tumor Activity of RO7284755, A PD-1 Targeted IL-2 Variant (IL-2V) Immunocytokine, Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
Actual Study Start Date : May 4, 2020
Estimated Primary Completion Date : April 4, 2024
Estimated Study Completion Date : August 13, 2024

Resource links provided by the National Library of Medicine


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 weekly.

Experimental: RO7284755 in Combination with Atezolizumab
Part 2: Dose-escalation of RO7284755 in combination with atezolizumab.
Drug: RO7284755
Participants will be administered RO7284755 weekly.

Drug: Atezolizumab
Participants will be administered 1200 mg of atezolizumab once every 3 weeks.
Other Name: Tecentriq

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 weekly.

Drug: Atezolizumab
Participants will be administered 1200 mg of atezolizumab once every 3 weeks.
Other Name: Tecentriq




Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events in Part 1 and Part 2 [ Time Frame: 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.

  2. Percentage of Participants with Dose-Limiting Toxicities [ Time Frame: 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.

  3. Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Part 3 [ Time Frame: 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).


Secondary Outcome Measures :
  1. Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Parts 1 and 2 [ Time Frame: 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).

  2. Percentage of Participants with Adverse Events in Part 3 [ Time Frame: 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.

  3. Disease Control Rate in Part 3 [ Time Frame: 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.

  4. Duration of Response in Part 3 [ Time Frame: 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.

  5. Progression-free survival (PFS) in Part 3 [ Time Frame: 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.

  6. Change from Baseline in Antidrug Antibody (ADA) to RO7284755 [ Time Frame: Up to 28 months ]
  7. Percentage of Partcipants with ADAs to RO7284755 [ Time Frame: Up to 28 months ]
  8. Area Under the Curve (AUC) for RO7284755 [ Time Frame: 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) ]
  9. Minimum Concentration (Cmin) for RO7284755 [ Time Frame: 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) ]
  10. Maximum Concentration (Cmax) for RO7284755 [ Time Frame: 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) ]
  11. Clearance (CL) for RO7284755 [ Time Frame: 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) ]
  12. Volume of Distribution at Steady-State Conditions (Vss) for RO7284755 [ Time Frame: 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) ]
  13. 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) [ Time Frame: Baseline ]
  14. Percentage of Immune Cells with CD8+ PD1+ and CD8+ PD1+ TCF7+ Expression [ Time Frame: Baseline ]
  15. Blood Tumor Mutational Burden [ Time Frame: Baseline ]
    Blood tumor mutational burden is defined as the number of genetic mutations per megabase (1,000,000 bases).

  16. Change from Baseline in Percentage of Immune Cell Subsets [ Time Frame: Baseline to End of Treatment (up to approximately 28 months) ]
    Immune cells include NK, CD8, and Treg cells

  17. Change from Baseline in Percentage of Immune Markers [ Time Frame: Baseline to End of Treatment (up to approximately 28 months) ]
    Immune markers include PD-1, PD-L1, sCD25, cytokines, etc...



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  • Eastern Cooperative Oncology Group Performance Status 0 to 1
  • Life expectancy of >=12 weeks
  • Consent to provide an archival tumor tissue sample
  • 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
  • Known active central nervous system (CNS) metastases
  • History of 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
  • Uncontrolled tumor-related pain or symptomatic hypercalcemia
  • Concurrent second malignancy
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
  • Episode of significant cardiovascular/cerebrovascular acute disease within 28 days before study treatment administration
  • Active or uncontrolled infections
  • Known HIV infection
  • Hepatitis B virus (HBV) or hepatitis C virus infection
  • 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
  • Participants with bilateral pleural effusion
  • Major surgery or significant traumatic injury < 28 days before study treatment administration or anticipation of the need for major surgery during study treatment
  • 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
  • History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04303858


Contacts
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Contact: BP41628 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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Belgium
Cliniques Universitaires St-Luc Recruiting
Bruxelles, Belgium, 1200
UZ Leuven Gasthuisberg Recruiting
Leuven, Belgium, 3000
Canada, Ontario
Princess Margaret Cancer Center; Department of Radiation Oncology Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Denmark
Herlev Hospital; Afdeling for Kræftbehandling Recruiting
Herlev, Denmark, 2730
Rigshospitalet; Fase 1 Enhed - Onkologi Recruiting
København Ø, Denmark, 2100
Netherlands
NKI/AvL Not yet recruiting
Amsterdam, Netherlands, 1066 CX
Erasmus MC Not yet recruiting
Rotterdam, Netherlands, 3015 GD
Poland
Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz Recruiting
Gdańsk, Poland, 80-214
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz Recruiting
Warszawa, Poland, 02-781
Spain
Clinica Universitaria de Navarra; Servicio de Oncologia Recruiting
Pamplona, Navarra, Spain, 31008
Hospital del Mar; Servicio de Oncologia Not yet recruiting
Barcelona, Spain, 08003
Hospital Univ Vall d'Hebron; Servicio de Oncologia Recruiting
Barcelona, Spain, 08035
START Madrid-FJD, Hospital Fundacion Jimenez Diaz Recruiting
Madrid, Spain, 28040
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04303858    
Other Study ID Numbers: BP41628
2019-004022-25 ( EudraCT Number )
First Posted: March 11, 2020    Key Record Dates
Last Update Posted: June 5, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Atezolizumab
Antineoplastic Agents