Clinical trial NCT04303858: A Study to Evaluate Safety and Anti-Tumor Activity of Eciskafusp Alfa (RO7284755) Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-03-11
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an entry-into-human study and will assess the effects of eciskafusp alfa (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.

Detailed description: The study consists of three parts: dose-escalation of eciskafusp alfa as a single agent (Part 1), dose-escalation of eciskafusp alfa in combination with atezolizumab (Part 2), and extension of eciskafusp alfa as a single agent and/or in combination with atezolizumab (Part 3).

Eligibility criteria: Inclusion Criteria:

* Locally advanced/unresectable or metastatic disease
* No standard of care (SoC) (approved) treatments are available for the participant, or the participant cannot tolerate such treatments
* 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
* Untreated central nervous system (CNS) metastases
* 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
* 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. In Part 3, patients who have received adoptive cell therapy such as tumor-infiltrating lymphocytes (TIL) are excluded.

Primary outcomes:
measure: Percentage of Participants with Adverse Events in Part 1 and Part 2
timeFrame: From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)
measure: Percentage of Participants with Dose-Limiting Toxicities in Part 1 and Part 2
timeFrame: From randomization up to day 14 (Part 1) or day 28 (Part 2)
measure: Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Part 3
timeFrame: From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
measure: Recommended Dose for Extension (RDE) of Eciskafusp Alfa in Parts 1 and 2
timeFrame: From randomization up to day 14 (Part 1) or day 28 (Part 2)
Secondary outcomes:
measure: Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Parts 1 and 2
timeFrame: From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)
measure: Percentage of Participants with Adverse Events in Part 3
timeFrame: From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
measure: Disease Control Rate in Part 3
timeFrame: From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
measure: Duration of Response in Part 3
timeFrame: From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
measure: Progression-free survival (PFS) in Part 3
timeFrame: From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
measure: Change from Baseline in Antidrug Antibody (ADA) to Eciskafusp Alfa
timeFrame: Up to 28 months
measure: Percentage of Partcipants with ADAs to Eciskafusp Alfa
timeFrame: Up to 28 months
measure: Area Under the Curve (AUC) for Eciskafusp Alfa
timeFrame: 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)
measure: Minimum Concentration (Cmin) for Eciskafusp Alfa
timeFrame: 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)
measure: Maximum Concentration (Cmax) for Eciskafusp Alfa
timeFrame: 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)
measure: Clearance (CL) for Eciskafusp Alfa
timeFrame: 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)
measure: Volume of Distribution at Steady-State Conditions (Vss) for Eciskafusp Alfa
timeFrame: 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)
measure: 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)
timeFrame: Baseline
measure: Percentage of Immune Cells with CD8+ PD1+ and CD8+ PD1+ TCF7+ Expression
timeFrame: Baseline
measure: Blood Tumor Mutational Burden
timeFrame: Baseline
measure: Change from Baseline in Percentage of Immune Cell Subsets
timeFrame: Baseline to End of Treatment (up to approximately 28 months)
measure: Change from Baseline in Percentage of Immune Markers
timeFrame: Baseline to End of Treatment (up to approximately 28 months)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Herlev
country: Denmark
facility: Herlev Hospital
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundacion Jimenez Diaz
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: