Clinical Trials /

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

NCT03539484

Description:

This study will 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 will be conducted in two parts. Part I of the study will consist of an IV single participant cohort/multiple-ascending dose-escalation to evaluate the safety of RO7172508. Part II is 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 will switch from Part I to Part II when the maximum planned dose for Part I is reached or the occurrence of a RO7172508-related Grade >= 2 adverse event (AE) or dose-limiting toxicity (DLT) is 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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors
  • Official Title: A First-in-Human, Open-Label, Multicenter, Dose-Escalation Phase I Clinical Study of Single-Agent RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BP40092
  • NCT ID: NCT03539484

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
RO7172508Part I: Single Participant Cohorts IV/MAD-Escalation

Purpose

This study will 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 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 will be conducted in two parts. Part I of the study will consist of an IV single participant cohort/multiple-ascending dose-escalation to evaluate the safety of RO7172508. Part II is 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 will switch from Part I to Part II when the maximum planned dose for Part I is reached or the occurrence of a RO7172508-related Grade >= 2 adverse event (AE) or dose-limiting toxicity (DLT) is 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.

Trial Arms

NameTypeDescriptionInterventions
Part I: Single Participant Cohorts IV/MAD-EscalationExperimentalPart I is a multiple-ascending dose-escalation in single participant cohorts. RO7172508 will be administered IV once every 3 weeks (Q3W). The starting dose of RO7172508 will be 65 microgram (mcg) and the maximum dose explored will be 1.6 milligram (mg).
  • RO7172508
Part II: Multiple Participant Cohorts IV/MAD-EscalationExperimentalMultiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation will be determined by Part I and RO7172508 will be initially given Q3W. Dose-escalation will be undertaken based on safety until determination of the MTD or the highest safe dose if MTD is not reached. If on-target toxicity is reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.
  • RO7172508
Part II: Multiple Participant Cohorts SC/MAD-Escalation (QW)ExperimentalMultiple 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 greater than 6 mg. SC dosing will be once a week (QW). The starting-dose for SC administration will be proposed based on the evaluation of the safety and PK data observed following IV administration. Dose escalation in this arm will proceed until the SC MTD/OBD has been determined. If on-target toxicity is reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.
  • RO7172508

Eligibility Criteria

        Inclusion Criteria:

          -  For Part I: participants with locally advanced and/or metastatic solid tumor with
             confirmed cytoplasmic and/or membranous high CEA expression in tumor tissue is
             required. Participants must have progressed on a SOC therapy, be intolerant to SOC,
             and/or are non-amenable to SOC.

          -  For Part I: CEA levels below a certain threshold is required as follows:

               -  For dose cohorts 65-159 microgram, a sCEA level of < 22 ng/mL

               -  For dose cohorts 160-399 microgram, a sCEA level of < 28 ng/mL

               -  For dose cohorts 400-799 microgram, a sCEA level of < 44 ng/mL

               -  For dose cohorts 800-1599 microgram, a sCEA level of < 70 ng/mL

               -  For the dose cohort of 1.6 milligramg, a sCEA level of < 123 ng/mL

          -  For Part II, participants with locally advanced and/or metastatic solid tumor
             expressing cytoplasmic and/or membranous high-CEA or moderate/low-CEA on archival
             material, who have progressed on a SOC therapy, are intolerant to SOC, and/or are
             non-amenable to SOC. Participants must have a lesion amenable to biopsy (except
             participants with NSCLC, which may be enrolled with archival tissue available only).

          -  Radiologically measurable disease according to RECIST v1.1.

          -  Life expectancy of >= 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.

          -  All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure
             must have resolved to Grade <= 1 or returned to baseline except alopecia (any grade)
             and Grade 2 peripheral neuropathy.

          -  Adequate hematological, liver, renal, and lung function

          -  For women: agree to remain abstinent or use two contraceptive methods that result in a
             failure rate of <1% per year from screening until 2 months after the last dose of
             RO7172508 and have a negative pregnancy test within one week prior to the first study
             treatment administration

          -  For men: remain abstinent or use contraceptive measures such as a condom plus an
             additional contraceptive method that together result in a failure rate of <1% per
             year, with partners who are woman of childbearing potential and refrain from donating
             sperm during the study

        Exclusion Criteria:

          -  History or clinical evidence of central nervous system (CNS) primary tumors or
             metastases unless they have been previously treated, are asymptomatic, and have had no
             requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days before
             screening.

          -  Non-irradiated lesions > 2 cm at critical sites where tumor swelling induced by
             RO7172508 is expected to lead to significant complications.

          -  Another invasive malignancy in the last 2 years

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results or contraindicate the use of
             an investigational drug.

          -  Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac
             arrhythmia that requires treatment with the exceptions of atrial fibrillation and
             paroxysmal supraventricular tachycardia, and history of myocardial infarction within 6
             months of enrollment.

          -  Active or uncontrolled infections.

          -  Known hepatitis B or C

          -  Major surgery or significant traumatic injury < 28 days prior to the first RO7172508
             administration or anticipation of the need for major surgery during study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Dose Limiting Toxicities (DLTs)
Time Frame:Part 1: C1D1 to C1D7, Part 2: C1D1 to C1D21
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum concentration of RO7172508
Time Frame:P1:D1-3,8,15 of C1; D1,8,15 of C2-3; D1,8 of C4 OW; P2(IV/MAD): D1- 3,8,15 of C1-2; D1,3,8,15 of C3- 4; D1, 3,15 of C5 OW; P2(SC,QW): D1-3,5,8,10,15,17 of C1; D1,5,8,15 of C2 OW; P2 (IV cohort): D1-3,8,9,15,16 of C1; D1,3,8,15 of C2-4; D1, 3,15 of C5 OW
Safety Issue:
Description:Part (P), Day (D), Cycle (C) is 21 days, onwards (OW), Multiple Ascending Dose (MAD)
Measure:Time of maximum concentration of RO7172508
Time Frame:P1:D1-3,8,15 of C1; D1,8,15 of C2-3; D1,8 of C4 OW; P2(IV/MAD): D1- 3,8,15 of C1-2; D1,3,8,15 of C3- 4; D1, 3,15 of C5 OW; P2(SC,QW): D1-3,5,8,10,15,17 of C1; D1,5,8,15 of C2 OW; P2 (IV cohort): D1-3,8,9,15,16 of C1; D1,3,8,15 of C2-4; D1, 3,15 of C5 OW
Safety Issue:
Description:Part (P), Day (D), Cycle (C) is 21 days, onwards (OW), Multiple Ascending Dose (MAD)
Measure:Clearance or apparent clearance of RO7172508
Time Frame:P1:D1-3,8,15 of C1; D1,8,15 of C2-3; D1,8 of C4 OW; P2(IV/MAD): D1- 3,8,15 of C1-2; D1,3,8,15 of C3- 4; D1, 3,15 of C5 OW; P2(SC,QW): D1-3,5,8,10,15,17 of C1; D1,5,8,15 of C2 OW; P2 (IV cohort): D1-3,8,9,15,16 of C1; D1,3,8,15 of C2-4; D1, 3,15 of C5 OW
Safety Issue:
Description:Part (P), Day (D), Cycle (C) is 21 days, onwards (OW), Multiple Ascending Dose (MAD)
Measure:Volume of distribution of RO7172508
Time Frame:P1:D1-3,8,15 of C1; D1,8,15 of C2-3; D1,8 of C4 OW; P2(IV/MAD): D1- 3,8,15 of C1-2; D1,3,8,15 of C3- 4; D1, 3,15 of C5 OW; P2(SC,QW): D1-3,5,8,10,15,17 of C1; D1,5,8,15 of C2 OW; P2 (IV cohort): D1-3,8,9,15,16 of C1; D1,3,8,15 of C2-4; D1, 3,15 of C5 OW
Safety Issue:
Description:Part (P), Day (D), Cycle (C) is 21 days, onwards (OW), Multiple Ascending Dose (MAD)
Measure:Area under the curve of RO7172508
Time Frame:P1:D1-3,8,15 of C1; D1,8,15 of C2-3; D1,8 of C4 OW; P2(IV/MAD): D1- 3,8,15 of C1-2; D1,3,8,15 of C3- 4; D1, 3,15 of C5 OW; P2(SC,QW): D1-3,5,8,10,15,17 of C1; D1,5,8,15 of C2 OW; P2 (IV cohort): D1-3,8,9,15,16 of C1; D1,3,8,15 of C2-4; D1, 3,15 of C5 OW
Safety Issue:
Description:Part (P), Day (D), Cycle (C) is 21 days, onwards (OW), Multiple Ascending Dose (MAD)
Measure:Half-life of RO7172508
Time Frame:P1:D1-3,8,15 of C1; D1,8,15 of C2-3; D1,8 of C4 OW; P2(IV/MAD): D1- 3,8,15 of C1-2; D1,3,8,15 of C3- 4; D1, 3,15 of C5 OW; P2(SC,QW): D1-3,5,8,10,15,17 of C1; D1,5,8,15 of C2 OW; P2 (IV cohort): D1-3,8,9,15,16 of C1; D1,3,8,15 of C2-4; D1, 3,15 of C5 OW
Safety Issue:
Description:Part (P), Day (D), Cycle (C) is 21 days, onwards (OW), Multiple Ascending Dose (MAD)
Measure:Presence or absence and titer of ADAs
Time Frame:Part 1: D1, 8, 15 of C1-3; D1 of C4 onwards; Part 2 IV/MAD and SC cohorts, IV cohort: D1, 8, 15 of C1-4; D1 of C5 onwards
Safety Issue:
Description:Cycle (C) is 21 days
Measure:Changes in frequency of tumor infiltrating lymphocytes
Time Frame:Part 2 IV/MAD and SC cohorts, IV cohort: Days 1, 8 of Cycles 1-4
Safety Issue:
Description:Cycle (C) is 21 days
Measure:Changes in activation status of tumor infiltrating lymphocytes
Time Frame:Part 2 IV/MAD and SC cohorts, IV cohort: Days 1, 8 of Cycles 1-4
Safety Issue:
Description:Cycle (C) is 21 days
Measure:Changes in spatial distribution of tumor infiltrating lymphocytes
Time Frame:Part 2 IV/MAD and SC cohorts, IV cohort: Days 1, 8 of Cycles 1-4
Safety Issue:
Description:Cycle (C) is 21 days
Measure:Objective response rate
Time Frame:Up to month 24
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:Up to month 24
Safety Issue:
Description:
Measure:Duration of response
Time Frame:Up to month 24
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:Up to month 24
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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