Clinical trial NCT04642365: A Study to Evaluate the Safety and Tolerability of RO7296682 in Combination With Atezolizumab in Participants With Advanced Solid Tumors.
Official title: An Open-Label, Multicenter, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of RO7296682 in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: RG6292
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-11-24
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability and preliminary anti-tumor activity of RO7296682 in combination with Atezolizumab in participants with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

- Diagnosis of advanced and/or metastatic solid tumors who have progressed on a standard therapy, are intolerant to standard of care (SoC), and/or and non-amenable to SoC.

Participants whose tumors have known sensitizing mutations must have experienced disease progression (during or after treatment) or intolerance to treatment with a respective targeted therapy.

* Measurable disease according to RECIST v1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Able to provide the most recent archival tumor tissue samples.
* Adequate cardiovascular, haematological, liver and renal function.
* Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen.
* Women of Childbearing Potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods.
* Men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods and refrain from donating sperm.

Exclusion Criteria:

* Pregnancy, lactation, or breastfeeding.
* Known hypersensitivity to any of the components of RO7296682 and atezolizumab, including but not limited to hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
* History or clinical evidence of central nervous system (CNS) primary tumors or metastases.
* Participants with another invasive malignancy in the last two years.
* Participants with known active or uncontrolled infection.
* Positive HIV test at screening.
* Positive for Hepatitis B and C.
* Vaccination with live vaccines within 28 days prior to C1D1.
* Major surgical procedure or significant traumatic injury within 28 days prior to first RO7296682 and atezolizumab infusion.
* Participants with wound healing complications.
* Dementia or altered mental status that would prohibit informed consent.
* History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash with eosinophilia and systemic symptoms).
* Active or history of autoimmune disease or immune deficiency.
* Prior treatment with CPIs (e.g. anti-CTLA4, anti-PD1, anti-PDL1), immunomodulatory monoclonal antibodies (mAbs) and/or mAb-derived therapies (approved or investigational) is approved.
* Treatment with standard radiotherapy, any chemotherapeutic agent, targeted therapy or treatment with any other investigational drug (defined as treatment for which there is currently no regulatory authority-approved indication) within 28 days or 5 half-lives of the drug (whichever is shorter), prior to the first RO7296882 administration on C1D1.
* Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy (for which no wash out period is required).

Primary outcomes:
measure: Part 1: Number of Participants With Adverse Events (AEs)
timeFrame: From Day 1 up to the end of safety follow-up (up to 28.5 months)
measure: Part 2: Number of Participants With AEs
timeFrame: From Day 1 up to the end of safety follow-up (up to 9.3 months)
measure: Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: From Cycle 1 Day 1 up Cycle 2 Day 8 (1 Cycle = 21 days)
measure: Part 2: Objective Response Rate (ORR)
timeFrame: Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
Secondary outcomes:
measure: Part 1: ORR
timeFrame: From Day 1 up to end of safety follow-up (up to 28.5 months)
measure: Part 1 and 2: Disease Control Rate (DCR)
timeFrame: Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
measure: Part 1 and 2: Duration of Response (DoR)
timeFrame: Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
measure: Part 1 and 2: Progression-Free Survival (PFS)
timeFrame: Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
measure: Part 1 and 2: Overall Survival (OS)
timeFrame: Part 1: From Day 1 up to end of survival follow-up (36 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
measure: Part 1 and 2: Area Under the Curve From Time of Dosing to the Last Timepoint at the End of the Dosing Period (AUClast) of RO7296682
timeFrame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
measure: Part 1 and 2: Maximum Concentration (Cmax) of RO7296682
timeFrame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
measure: Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682
timeFrame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
measure: Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682
timeFrame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
measure: Part 1 and 2: Half-life (t~1/2) of RO7296682
timeFrame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
measure: Part 1: Serum Concentration of Atezolizumab
timeFrame: Predose on Day 1 of Cycles 1 to 9, 12, 14, and 17; End of infusion (EOI) on Day 1 of Cycles 1 and 4; end of study/early discontinuation (up to 28.5 months)
measure: Part 1 and 2: Number of Participants With Treatment-induced Changes in T Regulatory C Ells (Treg) Levels in Blood and/or Tumor as Compared to Baseline
timeFrame: Baseline up to 28 days post last dose (up to 24.9 months)
measure: Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline
timeFrame: Cycle 1 Day 1 (end of infusion [EOI]); Cycle 1 Day 4 (72 hours post dose); Cycle 1 Day 8 (168 hours post dose); Cycle 1 Day 15 (336 hours post dose)
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute
state: Victoria
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: