Trial Title:
Tiragolumab and Atezolizumab in Advanced Pan-cancer Patients
NCT ID:
NCT06003621
Condition:
Solid Tumor, Adult
Conditions: Official terms:
Atezolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Prospective, multicentre, single-arm, open-label, phase II signal-seeking trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Tiragolumab
Description:
600mg IV every 21 days from Cycle 1 Day 1
Arm group label:
Tiragolumab and atezolizumab
Other name:
RO7092284
Other name:
MTIG7192A
Other name:
RG-6058
Other name:
Anti-TIGIT
Intervention type:
Biological
Intervention name:
Atezolizumab
Description:
1,200mg IV every 21 days from Cycle 2 Day 1
Arm group label:
Tiragolumab and atezolizumab
Other name:
Tecentriq
Other name:
MPDL3280A
Other name:
RG7446
Other name:
RO5541267
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.
Detailed description:
Patients who are enrolled in the MoST or CaSP cancer screening programs, and whose tumour
is assessed as amenable to tiragolumab and atezolizumab treatment, will be recommended
for participation in the study. After being informed about the study, and the potential
risks, patients who consent to participate undergo a 21-day screening period to determine
study eligibility. Patients will be prospectively selected into subgroups based on their
tumour characteristics.
Once eligibility is confirmed, tiragolumab alone is administered at Cycle 1 Day 1 (day 1
of study). Commencing from Cycle 2 Day 1, tiragolumab and atezolizumab are administered
at 21-day cycles until treatment discontinuation, with or without disease progression.
Participants undergo a biopsy at cycle 2 prior to commencement of atezolizumab treatment.
Standard imaging scans (usually computed tomography (CT)) are performed throughout the
trial. Patients also undergo blood, urine and stool sample collection on study.
Once participants discontinue treatment, a study visit is performed within 30 days of the
end of the final treatment cycle. If treatment cessation is not contemporaneous with
disease progression, follow-up calls are conducted every 9 weeks until disease
progression. Once disease progression occurs, a study visit is performed within 30 days
of disease progression and then every 3 months until 12 months after the final
participant discontinues study treatment.
Active follow-up of all participants will continue until death or 12 months after the
last participant discontinues study treatment, whichever occurs first. Subsequently,
survival data will be obtained through MoST or CaSP until death.
Criteria for eligibility:
Criteria:
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;
- tumour mutation burden ≥ 10 mutations per megabase.
- tumour PD-L1 expression TAP score ≥ 5%
- PD-L1 amplification >6 copy number alterations
- 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.
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 Fredericia's Correction.
6. 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.
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 (including, but not limited to,
interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is
longer) 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. No contraindication to study treatments as judged by the patient's responsible
clinician.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Border Medical Oncology Research Unit
Address:
City:
Albury
Zip:
2640
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Craig Underhill, MBBS, FRACP
Phone:
+61 2 6064 1515
Email:
Craig.Underhill@bordermedonc.com.au
Contact backup:
Last name:
Jacquiline McBurnie
Phone:
+61 2 6064 1508
Email:
jacqui.mcburnie@bordermedonc.com.au
Investigator:
Last name:
Craig Underhill, MBBS, FRACP
Email:
Principal Investigator
Facility:
Name:
Ramsay Health Care Australia Pty Ltd trading as The Border Cancer Hospital
Address:
City:
Albury
Zip:
2640
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Craig Underhill, MBBS, FRACP
Phone:
+61 2 6064 1515
Email:
Craig.Underhill@bordermedonc.com.au
Contact backup:
Last name:
Jacquiline McBurnie McBurnie
Phone:
+61 2 6064 1508
Email:
jcmburnie@bordermedonc.com.au
Investigator:
Last name:
Craig Underhill, MBBS, FRACP
Email:
Principal Investigator
Facility:
Name:
Coffs Harbour Health Campus
Address:
City:
Coffs Harbour
Zip:
2450
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Karen Briscoe, MD
Phone:
+61 2 6656 5737
Email:
karen.briscoe@health.nsw.gov.au
Contact backup:
Last name:
Joanne Smith, RN
Phone:
+61 2 6656 5053
Email:
joanne.smith10@health.nsw.gov.au
Facility:
Name:
Orange Base Hospital
Address:
City:
Orange
Zip:
2800
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Robert Zielinski, MD
Phone:
+61 2 63692333
Email:
rob.zielinski@health.nsw.gov.au
Contact backup:
Last name:
Ainslie Condon, RN
Phone:
+61 2 63693128
Email:
Ainslie.Condon@health.nsw.gov.au
Facility:
Name:
Port Macquarie Base Hospital
Address:
City:
Port Macquarie
Zip:
2444
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Stephen Begbie, MD
Phone:
+61 2 6581 4053
Email:
stephen.begbie@health.nsw.gov.au
Contact backup:
Last name:
Nikki Rooimans, RN
Phone:
+61 2 6581 4053
Email:
Nikki.Rooimans@health.nsw.gov.au
Facility:
Name:
Cairns Hospital
Address:
City:
Cairns
Zip:
4870
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Megan Lyle, MD
Phone:
+61 7 42267383
Email:
megan.lyle@health.qld.gov.au
Contact backup:
Last name:
Donna Kreuter
Phone:
+61 7 42268085
Email:
donna.kreuter@health.qld.gov.au
Facility:
Name:
Rockhampton Hospital
Address:
City:
Rockhampton
Zip:
4700
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Bahram Forouzesh, MD
Phone:
+61 7 49206541
Email:
bahram.forouzesh@health.qld.gov.au
Contact backup:
Last name:
Donna Reeves
Phone:
+61 436693407
Email:
donna.reeves@health.qld.gov.au
Facility:
Name:
Toowoomba Hospital
Address:
City:
Toowoomba
Zip:
4350
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Khageshwor Pokharel, MD
Phone:
+61 432 260 376
Email:
Khageshwor.Pokharel@health.qld.gov.au
Contact backup:
Last name:
Kerry Blacket
Phone:
+61 7 4616 5958
Email:
ToowoombaOncTrials@health.qld.gov.au
Facility:
Name:
Townsville Hospital
Address:
City:
Townsville
Zip:
4810
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Jun B Kong, MD
Phone:
+61 7 44337789
Email:
JB.Kong@health.qld.gov.au
Contact backup:
Last name:
Melanie Taylor
Phone:
+61 7 44333549
Email:
Melanie.Taylor@health.qld.gov.au
Facility:
Name:
Royal Hobart Hospital
Address:
City:
Hobart
Zip:
7000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Rosemary Harrup, MD
Phone:
03 6166 8157
Email:
rosemary.harrup@ths.tas.gov.au
Contact backup:
Last name:
Jamuna Chhetri
Phone:
03 6166 7921
Email:
jamuna.chhetri@ths.tas.gov.au
Facility:
Name:
Bendigo Health
Address:
City:
Bendigo
Zip:
3550
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Sam Harris, MD
Phone:
+61 3 5454 8815
Email:
sjharris@bendigohealth.org.au
Contact backup:
Last name:
Joanna Smith, RN
Phone:
+61 3 5454 8815
Email:
JMSmith@bendigohealth.org.au
Facility:
Name:
Barwon Health
Address:
City:
Geelong
Zip:
3220
Country:
Australia
Status:
Recruiting
Contact:
Last name:
David Campbell, MD
Phone:
+61 3 4215 2704
Email:
david.campbell@barwonhealth.org.au
Contact backup:
Last name:
Lauren Smith
Phone:
+61 3 4215 2811
Email:
Lauren.Smith@barwonhealth.org.au
Facility:
Name:
Fiona Stanley Hospital
Address:
City:
Perth
Zip:
6150
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Wei-Sen Lam, MD
Phone:
+61 8 6152 6721
Email:
Wei-Sen.Lam@health.wa.gov.au
Contact backup:
Last name:
Trish Barrett
Phone:
+61 8 6152 6721
Email:
Patricia.Barrett@health.wa.gov.au
Start date:
December 15, 2023
Completion date:
November 1, 2028
Lead sponsor:
Agency:
Omico
Agency class:
Other
Collaborator:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Collaborator:
Agency:
The George Institute for Global Health, Australia
Agency class:
Other
Source:
Omico
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06003621
