A Study of RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors

Sponsor
Hoffmann-La Roche
Study ID
NCT03539484
Phase
PHASE1
Status
Terminated

Conditions

  • Solid Tumors

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • RO7172508 — DRUG
    RO7172508 was administered at a dose and as per the schedule specified in the respective arms.
  • Obinutuzumab — DRUG
    In the event obinutuzumab treatment is implemented, obinutuzumab will be administered either on Day-7 or on Day-7 and Day-6. If obinutuzumab is given only on one day, then the schedule for Day-7 should be followed including an end of infusion sample.
  • Tocilizumab — DRUG
    Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)

Study Details

This study was to determine the maximum-tolerated dose (MTD) and/or the optimal biological dose (OBD) as well as the optimal schedule for intravenous (IV) and subcutaneous (SC) administrations of RO7172508 as monotherapy, with or without obinutuzumab pre-treatment, in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA)-positive solid tumors who have progressed on standard of care (SOC) treatment, are intolerant to SOC, and/or are non-amenable to SOC. This study was conducted in two parts. Part I of the study consisted of an IV single participant cohort/multiple-ascending dose-escalation to evaluate the safety of RO7172508. Part II was a multiple participant cohort/multiple-ascending dose-escalation to define the MTD and/or OBD of RO7172508 administered as single agent, IV and/or SC, in participants with tumors that are expressing high as well as moderate/low-CEA. The study switched from Part I to Part II when the maximum planned dose for Part I was reached or the occurrence of a RO7172508-related Grade \>= 2 adverse event (AE) or dose-limiting toxicity (DLT) was observed, whichever comes first. The Sponsor may decide to switch from Part I to Part II in the absence of an observed RO7172508-related Grade \>= 2 toxicity or prior to maximum planned dose for Part I.

Key Dates

Start date
Jul 4, 2018
Status verified
Aug 2020
Primary completion
Jul 22, 2019
Completion
Jul 22, 2019

Study Design

Enrollment
26 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Part I: Single Participant Cohorts IV/MAD-Escalation
    Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W). The starting dose of RO7172508 was 65 microgram (mcg) and the maximum dose explored was 1.6 milligram (mg).
  • Experimental: Part II: Multiple Participant Cohorts IV/MAD-Escalation
    Multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Dose-escalation was undertaken based on safety until determination of the MTD or the highest safe dose if MTD is not reached. If on-target toxicity was reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.
  • Experimental: Part II: Multiple Participant Cohorts SC/MAD-Escalation (QW)
    Multiple ascending dose-escalation of SC-administered RO7172508 in multiple participant cohorts. These will be initiated once the IV schedule has shown RO7172508 preliminary clinical activity or the MTD has been established and is equal to or above 2 mg. The starting-dose and regimen once a week or once every 3 weeks (QW or Q3W) for SC administration will be proposed based on the evaluation of the safety and PK data observed following IV administration but will not exceed the highest safe dose tested in the IV Q3W dose escalation; a minimum dose of 2 mg is defined for a single SC administration. In addition, the QW SC starting-dose will not exceed one third of the IV MTD or of the highest safe IV dose tested. Dose escalation will continue based on safety until determination of the MTD or the planned maximum dose of 400 mg. If on-target toxicity is reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.

Primary Outcome Measure

Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Up to approximately 12 months ]

Related Studies