Tiragolumab and Atezolizumab in Advanced Pan-cancer Patients

NCT06003621 | Recruiting Phase 2 DMC

• 1 other identifier: ML43743
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 13

Brief Summary

This phase II study will explore the effect of 2 monoclonal antibodies, tiragolumab and atezolizumab, in patients with locally advanced solid cancers which cannot be removed by surgery or have spread. Their cancers will have characteristics which may predict immune response to the study treatment. PD-L1 and TIGIT are immune receptors which can help cancers grow by evading the immune response and inhibiting the action of some immune cells. By blocking these receptors, tiragolumab and atezolizumab may work together to re-activate the body's anti-tumour immune response and kill cancer cells.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) rate at 6 Months

  The primary outcome, PFS rate at 6 months, is defined as the proportion of participants who are alive and progression free at 6 months from start of study treatment Radiological disease progression is defined according to modified Response Evaluation Criteria in Solid Tumours version 1.1 for immune-based therapeutics (iRECIST) or Response Assessment in Neuro-Oncology criteria (RANO). Clinical progression is defined as the development of: 1. Symptoms attributable to cancer progression; or 2. Initiation of other anticancer treatment for cancer; or 3. Significant deterioration of performance status not explained by treatment toxicities, co-morbidities, or radiological evidence of progression; or 4. Unequivocal development of new non-measurable disease that is not assessable according to iRECIST or RANO criteria.

  6 months

Secondary Outcomes (10)

• Objective tumour response rate (OTRR) as per iRECIST or RANO criteria

  iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 18 months

• The median duration of objective tumour response

  iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 18 months

• Median PFS

  iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 60 months

• To evaluate the duration of clinical benefit (DCB)

  iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 60 months

• To evaluate the overall survival (OS) rate at 12 months

  Cycle 1 Day 1 to 12 months

Study Arms (1)

Tiragolumab and atezolizumab

EXPERIMENTAL

96 patients will be treated with tiragolumab for one cycle (600mg IV over 60-90 minutes). At Cycle 2 Day 1, participants receive IV tiragolumab (600mg) and atezolizumab (1,200mg) over 60-90 minutes. Cycles of tiragolumab and atezolizumab repeat every 21 days, with infusion time decreased (if tolerable) until treatment discontinuation, with or without disease progression. Because of the heterogeneity of eligible cancer types, and lack of knowledge about relevant cut-offs for this combination, analysis will be performed prospectively to allocate patients into 4 subgroups based on the following tumour characteristics; * Group 1: TMB ≥ 10, assessed using NGS panel screening. n=24 * Group 2:Tumour and immune cell PD-L1 expression (TAP score) \> 20% high or PD-L1 (CD274) amplification, defined as gene copy number \> 6 on the panel. n=24 * Group 3: Tumour and immune cell PD-L1 expression (TAP score) 5% - 20% int. n=24 * Group 4: Tumour infiltrating lymphocytes CD3+CD8+ ≥ 5%. n=24

Biological: Tiragolumab; Biological: Atezolizumab

Interventions

Tiragolumab BIOLOGICAL

600mg IV every 21 days from Cycle 1 Day 1

Also known as: RO7092284, MTIG7192A, RG-6058, Anti-TIGIT

Tiragolumab and atezolizumab

Atezolizumab BIOLOGICAL

1,200mg IV every 21 days from Cycle 2 Day 1

Also known as: Tecentriq, MPDL3280A, RG7446, RO5541267

Tiragolumab and atezolizumab

Eligibility Criteria

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

You may qualify if:

• Provision of written informed consent.
• Aged ≥18 years old.
• Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumour.
• Exhausted all available standard therapy or not suitable for standard therapy (including targeted therapies) for the tumour.
• ECOG performance status score of 0-1.
• Sufficient and accessible tumour tissue for panel sequencing, PD-L1 and TIL testing, and tertiary objectives.
• Tumour biomarker criteria predictive of immune response defined by presence of one or more of the following;
• Group 1: tumour mutation burden ≥ 10 mutations per megabase.
• Group 2: PD-L1 amplification \>6 copy number alterations
• Group 3: tumour PD-L1 expression TAP score ≥ 5%
• Group 4: tumour infiltrating lymphocytes (TILs) (CD3+CD8+) ≥ 5%.
• Patient is willing to provide tumour biopsy samples on treatment at Week 4.
• Life expectancy \>12 weeks.
• Measurable disease as defined by iRECIST or RANO criteria.
• Adequate haematological and biochemical indices as defined by:

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Roche staff and/or staff at the study site).
• Patients with non-small cell lung cancer.
• Participation in another clinical study with an investigational product during the last 4 weeks prior to study enrolment.
• Any unresolved toxicity (\>CTCAE grade 2) from previous anti-cancer therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-α \[TNF-α\] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• topical, intranasal, or inhaled corticosteroids or systemic corticosteroids at or below physiological doses (eg. ≤10 mg/day of prednisone);
• use of dexamethasone up to 4mg/day within 14 days of initial treatment for patients with brain tumours.
• Symptomatic or actively progressing central nervous system (CNS) metastases.
• Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.
• The patient has no history of intracranial haemorrhage or spinal cord haemorrhage.
• The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease.
• If the patient is receiving anti-convulsant therapy, the dose is considered stable.

Sponsors & Collaborators

• Omico: lead
• Hoffmann-La Roche: collaborator
• The George Institute for Global Health, Australia: collaborator

Study Sites (13)

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

RECRUITING

Ramsay Health Care Australia Pty Ltd trading as The Border Cancer Hospital

Albury, New South Wales, 2640, Australia

RECRUITING

Coffs Harbour Health Campus

Coffs Harbour, New South Wales, 2450, Australia

RECRUITING

Orange Base Hospital

Orange, New South Wales, 2800, Australia

RECRUITING

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

RECRUITING

Cairns Hospital

Cairns, Queensland, 4870, Australia

NOT YET RECRUITING

Rockhampton Hospital

Rockhampton, Queensland, 4700, Australia

NOT YET RECRUITING

Toowoomba Hospital

Toowoomba, Queensland, 4350, Australia

NOT YET RECRUITING

Townsville Hospital

Townsville, Queensland, 4810, Australia

RECRUITING

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

RECRUITING

Bendigo Health

Bendigo, Victoria, 3550, Australia

RECRUITING

Barwon Health

Geelong, Victoria, 3220, Australia

RECRUITING

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

RECRUITING

MeSH Terms

Interventions

Tiragolumab; atezolizumab

Study Officials

• David Thomas, PHD, FRACP

  Omico; UNSW Sydney

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simone Jacoby

CONTACT

+61 2 8052 4300; most-tap@georgeinstitute.org.au

Vanessa Jones

CONTACT

+61 2 8052 4300; most-tap@georgeinstitute.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, multicentre, single-arm, open-label, phase II signal-seeking trial

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: August 22, 2023
• Study Start: December 15, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: November 15, 2024

Record last verified: 2024-06

Locations

AU (13)