A PHASE I, OPEN-LABEL, MULTICENTER, DOSE-ESCALATION STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, AND ACTIVITY OF RO7566802 AS A SINGLE AGENT AND IN COMBINATION WITH ATEZOLIZUMAB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS (GO44431)

Research summary

This is a first-in-human Phase I, open-label, multicenter, dose-escalation and expansion study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumour activity of RO7566802 as a single agent and in combination with atezolizumab in patients with locally advanced, recurrent, or metastatic incurable solid tumour malignancies. The study consists of a screening period of up to 28 days, a treatment period, a minimum follow-up period of 90 days after treatment, and survival follow-up. Patients will be enrolled in two stages: a dose-escalation stage and an expansion stage. During the dose-escalation stage, cohorts of 3-6 all-comer patients each will be evaluated at escalating dose levels to determine the MTD (maximum tolerated dose) or maximum administered dose (MAD) for RO7566802 in combination with atezolizumab. Once the MTD or MAD has been established, additional patients will be enrolled in the expansion stage and treated at or below the MTD or MAD. Approximately 20-70 patients (inclusive of backfills) will be enrolled in the dose-escalation stage. The starting dose of RO7566802 in the dose-escalation stage will be 60 mg, administered IV every 3 weeks (Q3W). Treatment cycles will be 21 days in length. Patients enrolled in the dose-escalation cohorts will receive one cycle of RO7566802 as a single agent at Cycle 1 Day 1 (“run-in” dosing) followed by RO7566802 in combination with atezolizumab (starting at Cycle 2), every 3 weeks thereafter. The Sponsor Safety Monitoring Committee (SMC) will review the safety data and perform DLT evaluations during the dose-escalation stage. The DLT assessment window for dose escalation will be from Cycle 1 Day 1 through 21 days after Cycle 2 Day 1, regardless of dose delays. DLT evaluation will not be assessed for patients enrolled in the backfill cohorts. Up to approximately 50 patients with ovarian, clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), melanoma, endometrial cancer, and cholangiocarcinoma may be enrolled in backfill cohorts at dose levels that do not exceed the last cleared dose (up to 10 patients in each dose-level cohort). Up to approximately half of patients enrolled in each backfill cohort will undergo a mandatory serial biopsy (pretreatment and on-treatment biopsies). All patients enrolled in the backfill cohorts will receive RO7566802 in combination with atezolizumab (“concurrent” dosing) starting at Cycle 1 and at subsequent cycles. In the expansion stage (PD-L1-selected cohorts), approximately 60-100 patients with ovarian cancer or ccRCC will be enrolled and treated at or below the MTD or MAD of RO7566802 in combination with atezolizumab. All expansion patients will receive RO7566802 in combination with atezolizumab (“concurrent” dosing) starting at Cycle 1 and at subsequent cycles. The expansion stage of this study will be activated only after the Internal Monitoring Committee (IMC) reviews all relevant safety data, which will be performed in consultation with the Principal Investigators, as needed. Patients enrolling into expansion cohorts can have tumour tissue screening for PD-L1 status performed prior to the 28-day screening period. Patients who discontinue RO7566802 and atezolizumab for disease progression and are not eligible to continue treatment past disease progression will return to the clinic for a treatment discontinuation visit within 30 days after the final dose of study treatment. All patients will be closely monitored for adverse events throughout the study and for at least 90 days after the final dose of study treatment or until initiation of another systemic anti-cancer therapy, whichever occurs first. All patients in the study will be followed for survival and subsequent anti-cancer therapy information approximately every 3 months (from the last dose) until death, loss to follow-up, or until Sponsor decision to discontinue survival follow-up because no further clinical development of RO7566802 is planned or the study is terminated by the Sponsor, unless the patient requests to be withdrawn from follow-up.

Principal Investigator

Dr Eileen Parkes

Contact us

Email: orh-tr.earlyphasenurses@nhs.net

IRAS number

1008627