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

NCT05129280 | Terminated Phase 1 FDA Drug

• 2 other identifiers: BE432442021-000624-35
• Study Type: interventional
• Target: 23
• Locations: 6 countries
• Sites: 10

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  From start of treatment up to 21-28 days

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  From baseline up to 12 months

• Disease Control Rate (DCR)

  From baseline up to 12 months

• 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)

• 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)

• Overall Survival (OS)

  From baseline to death from any cause (up to 40 months)

Study Arms (3)

Part I: Single Participant Cohort (SPC) Dose Escalation

EXPERIMENTAL

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; Drug: Tocilizumab

Part II: Multiple Participant Cohort (MPC) Dose Escalation

EXPERIMENTAL

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; Drug: Tocilizumab

Part III: Recommended Phase 2 Dose (RP2D) Expansion

EXPERIMENTAL

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

Drug: RO7444973; Drug: Tocilizumab

Interventions

RO7444973 DRUG

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

Part I: Single Participant Cohort (SPC) Dose Escalation; Part II: Multiple Participant Cohort (MPC) Dose Escalation; Part III: Recommended Phase 2 Dose (RP2D) Expansion

Tocilizumab DRUG

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.

Also known as: Actemra, RoActemra

Part I: Single Participant Cohort (SPC) Dose Escalation; Part II: Multiple Participant Cohort (MPC) Dose Escalation; Part III: Recommended Phase 2 Dose (RP2D) Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Rigshospitalet; Fase 1 Enhed - Onkologi

København Ø, 2100, Denmark

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Hospital Universitario HM Sanchinarro-CIOCC

Madrid, 28050, Spain

Location

Royal Marsden Hospital - Institute of Cancer Research - Sutton

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Interventions

tocilizumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: November 22, 2021
• Study Start: January 25, 2022
• Primary Completion: July 12, 2023
• Study Completion: July 12, 2023
• Last Updated: August 4, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

DK (1); GB (1); US (1); AU (1); ES (2); BE (4)