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A Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-tumor Activity of RO7444973 in Participants With Unresectable and/or Metastatic MAGE-A4-positive Solid Tumors

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05129280
Collaborator
(none)
260
Enrollment
11
Locations
3
Arms
57.1
Anticipated Duration (Months)
23.6
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first-in-human, open-label, uncontrolled, multi-center, monotherapy dose-escalation and dose expansion study of RO7444973.The aim of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RO7444973 in participants with unresectable and/or metastatic melanoma-associated antigen A4 (MAGE-A4)-positive, solid tumors, carrying the HLA-A*02:01 allele.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
260 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Multicenter, Phase I Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-tumor Activity of RO7444973 in Participants With Unresectable and/or Metastatic MAGE-A4-positive Solid Tumors
Actual Study Start Date :
Jan 25, 2022
Anticipated Primary Completion Date :
Oct 30, 2026
Anticipated Study Completion Date :
Oct 30, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part I: Single Participant Cohort (SPC) Dose Escalation

In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.

Drug: RO7444973
RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.

Drug: Tocilizumab
Tocilizumab will be used as rescue therapy, in case of clinical presentation of cytokine release syndrome (CRS). Tocilizumab solution for infusion will be administered intravenously at 8 mg/kg for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.
Other Names:
  • Actemra, RoActemra

    		•
    Experimental: Part II: Multiple Participant Cohort (MPC) Dose Escalation

    In Part II, RO7444973 is administered IV Q3W at a fixed dose in multiple participants per dose level. Step-up dosing may also be explored.

    Drug: RO7444973
    RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.

    Drug: Tocilizumab
    Tocilizumab will be used as rescue therapy, in case of clinical presentation of cytokine release syndrome (CRS). Tocilizumab solution for infusion will be administered intravenously at 8 mg/kg for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.
    Other Names:
  • Actemra, RoActemra

    		•
    Experimental: Part III: Recommended Phase 2 Dose (RP2D) Expansion

    Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.

    Drug: RO7444973
    RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.

    Drug: Tocilizumab
    Tocilizumab will be used as rescue therapy, in case of clinical presentation of cytokine release syndrome (CRS). Tocilizumab solution for infusion will be administered intravenously at 8 mg/kg for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.
    Other Names:
  • Actemra, RoActemra

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From start of treatment up to 90 days after last RO7444973 dose (up to 15 months)]

    2. Number of Participants With Dose-limiting Toxicities (DLTs) [From start of treatment up to 21-28 days]

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) [From baseline up to 12 months]

    2. Disease Control Rate (DCR) [From baseline up to 12 months]

    3. Duration of Response (DoR) [From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 40 months)]

    4. Progression-free Survival (PFS) [From baseline to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 40 months)]

    5. Overall Survival (OS) [From baseline to death from any cause (up to 40 months)]

    6. Pharmacokinetics (PK): Serum Concentration of RO7444973 Over Time [From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months)]

    7. Change from Baseline in Percentage of Participants Positive for Anti-drug Antibodies (ADA) to RO7444973 [From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Unresectable and/or metastatic solid tumors that have received standard-of-care (SOC) therapies previously and have no other SOC options available

    • Confirmed HLA-A*02:01 haplotype

    • Confirmed MAGE-A4 expression

    • Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    • Life expectancy of >/=12 weeks

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

    • Absence of rapid disease progression, threat to vital organs or non-irradiated lesions

    2 cm in diameter at critical sites

    • No significant ongoing toxicity from prior anticancer treatment

    • Adequate hematological function

    • Adequate liver function

    • Adequate renal function

    • If applicable, willingness to use contraceptive measures.

    Key Exclusion Criteria:

    • History or clinical evidence of CNS primary tumors or metastases

    • Another invasive malignancy in the last 2 years

    • Uncontrolled hypertension

    • Significant cardiovascular disease

    • Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic or other infection

    • Current or past history of CNS disease

    • Dementia or altered mental status that would prohibit informed consent

    • Active auto-immune disease or flare within 6 months prior to start of study treatment

    • Expected need for regular immunosuppressive therapy or with systemic corticosteroids

    • Insufficient washout from prior anti-cancer therapy

    • Prior treatment with a bispecific T-cell engaging or adoptive cell therapy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    2 Peter Maccallum Cancer Centre Melbourne Victoria Australia 3000
    3 Cliniques Universitaires St-Luc Bruxelles Belgium 1200
    4 UZ Antwerpen Edegem Belgium 2650
    5 UZ Gent Gent Belgium 9000
    6 UZ Leuven Gasthuisberg Leuven Belgium 3000
    7 Rigshospitalet; Fase 1 Enhed - Onkologi København Ø Denmark 2100
    8 Clinica Universitaria de Navarra; Servicio de Oncologia Pamplona Navarra Spain 31008
    9 Vall d´Hebron Institute of Oncology (VHIO), Barcelona Barcelona Spain 08035
    10 Hospital Universitario HM Sanchinarro-CIOCC Madrid Spain 28050
    11 Royal Marsden Hospital - Institute of Cancer Research - Sutton Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT05129280
    Other Study ID Numbers:
    • BE43244
    • 2021-000624-35
    First Posted:
    Nov 22, 2021
    Last Update Posted:
    Aug 3, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    No Results Posted as of Aug 3, 2022