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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05129280




Registration number
NCT05129280
Ethics application status
Date submitted
19/11/2021
Date registered
22/11/2021
Date last updated
4/08/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2021-000624-35
Secondary ID [2] 0 0
BE43244
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RO7444973
Treatment: Drugs - Tocilizumab

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.

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.

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.


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

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
From start of treatment up to 90 days after last RO7444973 dose (up to 15 months)
Primary outcome [2] 0 0
Number of Participants With Dose-limiting Toxicities (DLTs)
Timepoint [2] 0 0
From start of treatment up to 21-28 days
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From baseline up to 12 months
Secondary outcome [2] 0 0
Disease Control Rate (DCR)
Timepoint [2] 0 0
From baseline up to 12 months
Secondary outcome [3] 0 0
Duration of Response (DoR)
Timepoint [3] 0 0
From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 40 months)
Secondary outcome [4] 0 0
Progression-free Survival (PFS)
Timepoint [4] 0 0
From baseline to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 40 months)
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
From baseline to death from any cause (up to 40 months)
Secondary outcome [6] 0 0
Pharmacokinetics (PK): Serum Concentration of RO7444973 Over Time
Timepoint [6] 0 0
From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months)
Secondary outcome [7] 0 0
Change from Baseline in Percentage of Participants Positive for Anti-drug Antibodies (ADA) to RO7444973
Timepoint [7] 0 0
From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months)

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/07/2023
Sample size
Target
Accrual to date
Final
23
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Edegem
Country [4] 0 0
Belgium
State/province [4] 0 0
Gent
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Denmark
State/province [6] 0 0
København Ø
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
Madrid
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05129280
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05129280