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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06003621




Registration number
NCT06003621
Ethics application status
Date submitted
7/08/2023
Date registered
22/08/2023

Titles & IDs
Public title
Tiragolumab and Atezolizumab in Advanced Pan-cancer Patients
Scientific title
A Single Arm, Open-label, Phase II Signal-seeking Trial of Tiragolumab and Atezolizumab in Patients With Advanced Solid Tumours.
Secondary ID [1] 0 0
ML43743
Universal Trial Number (UTN)
Trial acronym
MoST-TAP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor, Adult 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Tiragolumab
Treatment: Other - Atezolizumab

Experimental: Tiragolumab and atezolizumab - 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


Treatment: Other: Tiragolumab
600mg IV every 21 days from Cycle 1 Day 1

Treatment: Other: Atezolizumab
1,200mg IV every 21 days from Cycle 2 Day 1
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) rate at 6 Months
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Objective tumour response rate (OTRR) as per iRECIST or RANO criteria
Timepoint [1] 0 0
iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 18 months
Secondary outcome [2] 0 0
The median duration of objective tumour response
Timepoint [2] 0 0
iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 18 months
Secondary outcome [3] 0 0
Median PFS
Timepoint [3] 0 0
iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 60 months
Secondary outcome [4] 0 0
To evaluate the duration of clinical benefit (DCB)
Timepoint [4] 0 0
iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 60 months
Secondary outcome [5] 0 0
To evaluate the overall survival (OS) rate at 12 months
Timepoint [5] 0 0
Cycle 1 Day 1 to 12 months
Secondary outcome [6] 0 0
To calculate the median overall survival
Timepoint [6] 0 0
Cycle 1 Day 1 to death, up to 5 years
Secondary outcome [7] 0 0
To evaluate the time to progression (TTP)
Timepoint [7] 0 0
iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 60 months
Secondary outcome [8] 0 0
To calculate the median Growth Modulation Index (GMI)
Timepoint [8] 0 0
iRECIST/RANO every 9 weeks from study entry to objective disease progression, up to 60 months
Secondary outcome [9] 0 0
The incidence and rates of AEs and serious AEs (SAEs)
Timepoint [9] 0 0
From Cycle 1 Day 1 to 90 days after cessation of study drug
Secondary outcome [10] 0 0
To evaluate the health related quality of life (HRQOL) over the course of the trial
Timepoint [10] 0 0
Cycle 1 Day 1, Cycle 4 Day 1 and then every third cycle until disease progression (cycles length 21 days). Also administered at the Treatment Discontinuation Visit and the Progressive Disease Visit.

Eligibility
Key inclusion criteria
1. Provision of written informed consent.
2. Aged =18 years old.
3. Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumour.
4. Exhausted all available standard therapy or not suitable for standard therapy (including targeted therapies) for the tumour.
5. ECOG performance status score of 0-1.
6. Sufficient and accessible tumour tissue for panel sequencing, PD-L1 and TIL testing, and tertiary objectives.
7. 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%.
8. Patient is willing to provide tumour biopsy samples on treatment at Week 4.
9. Life expectancy >12 weeks.
10. Measurable disease as defined by iRECIST or RANO criteria.
11. Adequate haematological and biochemical indices as defined by:

* Absolute neutrophil count =1.0 x 10^9/L
* Haemoglobin =100 g/L
* Platelet count =100 x 10^9/L
* Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5x ULN; or =5.0x ULN if liver metastases are present.
* International normalised ratio (INR) <1.3 in the absence of anticoagulation therapy.
* Serum creatinine clearance >40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
12. Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count = 200cells/mm3 , and have an undetectable viral load.
13. Negative hepatitis B surface antigen (HBsAg) test at screening.
14. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following:

* Negative total hepatitis B core antibody (HBcAb);
* Positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL.

The HBV DNA test must be performed for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.
15. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test.
16. Women of childbearing potential must have a negative screening serum pregnancy test within 14 days prior to the first dose of study medication.
17. Women of childbearing potential and men must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the study and for at least 5 months after the last dose of study medication.
18. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements and instructions from study staff.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Involvement in the planning and/or conduct of the study (applies to both Roche staff and/or staff at the study site).
2. Patients with non-small cell lung cancer.
3. Participation in another clinical study with an investigational product during the last 4 weeks prior to study enrolment.
4. 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).
5. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
6. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-a [TNF-a] 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.
7. 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.
* Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
* There is no evidence of interim progression between completion of CNS directed therapy (if administered) and initiation of study treatment.

Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy and/or surgery, with no need to repeat the screening brain scan.
8. Prior use of approved or investigational anti-TIGIT therapy.
9. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
10. Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment.
11. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
12. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

* Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
* Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

i. Rash must cover < 10% of body surface area; ii. Disease is well controlled at baseline and requires only low-potency topical corticosteroids; and iii. There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
13. Active or prior documented inflammatory bowel disease requiring systemic treatment within the past 2 years (e.g., Crohn's disease, ulcerative colitis).
14. History of primary immunodeficiency.
15. History of allogeneic organ transplant.
16. History of hypersensitivity to mAb to PD1/PD-L1 or any excipient.
17. Uncontrolled intercurrent illness including, but not limited to:

* Ongoing or active infection
* Symptomatic congestive heart failure
* Uncontrolled hypertension
* Unstable angina pectoris
* Cardiac arrhythmia
* Active peptic ulcer disease or gastritis
* Active bleeding diatheses
* Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrolment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.

Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy, if appropriate, prior to enrolment.
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX®) are allowed.
* Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL, or corrected calcium greater than ULN)
* Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
18. Active tuberculosis.
19. Positive EBV viral capsid antigen (VCA) IgM test during screening. An EBV polymerase chain reaction (PCR) test should be performed as clinically indicated to screen for acute infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded.
20. History of leptomeningeal carcinomatosis.
21. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
22. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
23. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving tiragolumab and atezolizumab.
24. Pregnant or breastfeeding.
25. Contraindication to study treatments as judged by the patient's responsible clinician.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2028
Actual
Sample size
Target
96
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [2] 0 0
Ramsay Health Care Australia Pty Ltd trading as The Border Cancer Hospital - Albury
Recruitment hospital [3] 0 0
Coffs Harbour Health Campus - Coffs Harbour
Recruitment hospital [4] 0 0
Orange Base Hospital - Orange
Recruitment hospital [5] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [6] 0 0
Cairns Hospital - Cairns
Recruitment hospital [7] 0 0
Rockhampton Hospital - Rockhampton
Recruitment hospital [8] 0 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [9] 0 0
Townsville Hospital - Townsville
Recruitment hospital [10] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [11] 0 0
Bendigo Health - Bendigo
Recruitment hospital [12] 0 0
Barwon Health - Geelong
Recruitment hospital [13] 0 0
Fiona Stanley Hospital - Perth
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [3] 0 0
2800 - Orange
Recruitment postcode(s) [4] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [5] 0 0
4870 - Cairns
Recruitment postcode(s) [6] 0 0
4700 - Rockhampton
Recruitment postcode(s) [7] 0 0
4350 - Toowoomba
Recruitment postcode(s) [8] 0 0
4810 - Townsville
Recruitment postcode(s) [9] 0 0
7000 - Hobart
Recruitment postcode(s) [10] 0 0
3550 - Bendigo
Recruitment postcode(s) [11] 0 0
3220 - Geelong
Recruitment postcode(s) [12] 0 0
6150 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Omico
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Hoffmann-La Roche
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The George Institute for Global Health, Australia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Thomas, PHD, FRACP
Address 0 0
Omico; UNSW Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Simone Jacoby
Address 0 0
Country 0 0
Phone 0 0
+61 2 8052 4300
Fax 0 0
Email 0 0
most-tap@georgeinstitute.org.au
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Subject to further IRB review and protocol amendment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06003621