A Study to Explore the Efficacy and Safety of Atezolizumab Plus Tiragolumab and Chemotherapy in 1st Line HER2 Negative Unresectable, Recurrent or Metastatic Gastric Cancer or Adenocarcinoma of Gastroesophageal Junction (GEJ)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04933227

Collaborator

(none)

Enrollment

Locations

Arm

29.8

Anticipated Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate the efficacy and safety of atezolizumab plus tiragolumab in combination with capecitabine plus oxaliplatin (XELOX) for first-line treatment in participants with HER2-negative unresectable advanced, recurrent or metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJ AC).

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasms Gastric Cancer Gastroesophageal Junction Adenocarcinoma	Drug: Atezolizumab Drug: Tiragolumab Drug: Oxaliplatin Drug: Capecitabine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Single-Arm Study to Explore the Efficacy and Safety of Atezolizumab Plus Tiragolumab and Chemotherapy in 1st Line HER2 Negative Unresectable, Recurrent or Metastatic Gastric Cancer or Adenocarcinoma of Gastroesophageal Junction (GEJ)

Actual Study Start Date :

Aug 6, 2021

Anticipated Primary Completion Date :

Jul 7, 2023

Anticipated Study Completion Date :

Jan 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atezo + Tira + XELOX Atezolizumab plus tiragolumab in combination with XELOX (oxaliplatin and capecitabine) will be administered during Cycles 1-4 (each cycle is 21 days). During Cycle 5 and beyond atezolizumab and tiragolumab will be administered on Day 1 of each 21-day cycle. Participants will receive study treatment until disease progression, unacceptable toxicity or loss of clinical benefit as determined by the investigator.	Drug: Atezolizumab Atezolizumab 1200 mg will be administered intravenously (IV) on Day 1 of each 21-day cycle. Other Names: Tecentriq Drug: Tiragolumab Tiragolumab 600 mg will be administered IV on Day 1 of each 21-day cycle. Drug: Oxaliplatin Oxaliplatin 130 mg/m^2 will be administered IV on Day 1 of each 21-day cycle during Cycles 1-4. Drug: Capecitabine Capecitabine 1000 mg/m^2/d will be administered orally (PO) twice daily (bid) on Days 1-14 during Cycles 1-4.

Arm

Intervention/Treatment

Experimental: Atezo + Tira + XELOX

Atezolizumab plus tiragolumab in combination with XELOX (oxaliplatin and capecitabine) will be administered during Cycles 1-4 (each cycle is 21 days). During Cycle 5 and beyond atezolizumab and tiragolumab will be administered on Day 1 of each 21-day cycle. Participants will receive study treatment until disease progression, unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Atezolizumab

Atezolizumab 1200 mg will be administered intravenously (IV) on Day 1 of each 21-day cycle.

Other Names:

Tecentriq

Drug: Tiragolumab

Tiragolumab 600 mg will be administered IV on Day 1 of each 21-day cycle.

Drug: Oxaliplatin

Oxaliplatin 130 mg/m^2 will be administered IV on Day 1 of each 21-day cycle during Cycles 1-4.

Drug: Capecitabine

Capecitabine 1000 mg/m^2/d will be administered orally (PO) twice daily (bid) on Days 1-14 during Cycles 1-4.

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) in the Full Analysis Set (FAS) Population [Up to approximately 20 months]

Secondary Outcome Measures

Duration of Response (DOR) in Responders of the FAS Population [The time from the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months]
Progression-free Survival (PFS) in the FAS Population [The time from initiation of study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months]
Overall Survival (OS) in the FAS Population [The time from initiation of study treatment to death due to any cause up to approximately 20 months]
Mean Score in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in the FAS Population [Up to approximately 20 months]
Change from Baseline in EORTC QLQ-C30 in the FAS Population [Up to approximately 20 months]
Mean Score in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Gastric Cancer (EORTC QLQ-STO22) in the FAS Population [Up to approximately 20 months]
Change from Baseline in EORTC QLQ-STO22 in the FAS Population [Up to approximately 20 months]
ORR in a Subgroup Population With PD-L1 and/or TIGIT Positive Expression [Up to approximately 20 months]
Duration of Response (DOR) in Responders of a Subgroup Population With PD-L1 and/or TIGIT Positive Expression [The time from the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months]
Progression-free Survival (PFS) in a Subgroup Population With PD-L1 and/or TIGIT Positive Expression [The time from initiation of study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months]
Overall Survival (OS) in a Subgroup Population With PD-L1 and/or TIGIT Positive Expression [The time from initiation of study treatment to death due to any cause up to approximately 20 months]
Number of Participants With Adverse Events [Up to approximately 20 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed (by enrolling center) gastric cancer or adenocarcinoma of GEJ (Siewert I-III)
Unresectable locally advanced, unresectable recurrent, or metastatic disease that meets the following criteria: a) No prior systemic treatment for advanced disease, b) For patients receiving prior chemoradiotherapy or chemotherapy in the adjuvant or neoadjuvant setting, with an interval of at least 6 months between the final treatment and the diagnosis of advanced disease
Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as determined by investigator assessment
Availability of a representative tumor specimen that is suitable for determination of PD-L1 and TIGIT expression
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Life expectancy >/=3 months
Adequate hematologic and end-organ function
For women of childbearing potential: agreement to refrain from heterosexual intercourse or use contraception, and agreement to refrain from donating eggs
For men: agreement to refrain from heterosexual intercourse or use contraceptive methods, and agreement to refrain from donating sperm.

Exclusion Criteria:

HER2-positive by local review, defined as either immunohistochemistry (IHC) score of 3+ or IHC 2+ with amplification proven by in situ hybridization (ISH) as assessed based on pretreatment tumor tissues
Use of Chinese herbal medicine or Chinese patent medicines to control cancer within 7 days prior to initiation of study treatment
Higher risk of bleeding or fistula caused by GEJ Siewert I invading adjacent organs
Symptomatic, untreated, or actively progressing CNS metastases
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled or symptomatic hypercalcemia
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
Severe chronic or active infection within 4 weeks prior to initiation of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
Any other disease, medical condition, metabolic dysfunction, alcohol or drug abuse or dependence, physical examination finding, clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Prior treatment with CD137 agonists, T-cell co-stimulating, or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-TIGIT therapeutic antibodies
Treatment with systemic immunostimulatory agents or any investigational therapy within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
Known allergy or hypersensitivity to any component of atezolizumab, tiragolumab, capecitabine or oxaliplatin formulations
Pregnant or breastfeeding.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	China	100142
2	Jilin Cancer Hospital	Changchun	China	132013
3	Hunan Cancer Hospital	Changsha City	China	410013
4	Changzhou First People's Hospital	Changzhou	China	213003
5	The First Affiliated Hospital of College of Medicine, Zhejiang University; Medical Oncology	Hangzhou	China	310003
6	Anhui Province Cancer Hospital	Hefei	China	230000
7	The First Affiliated Hospital of Anhui Medical University	Hefei	China	230022
8	Liaoning cancer Hospital & Institute	Shenyang	China	110042
9	Tianjin Cancer Hospital	Tianjin	China	300060
10	Hubei Cancer Hospital	Wuhan	China	430079
11	The First Affiliated Hospital of Xiamen University	Xiamen	China	361003

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04933227

Other Study ID Numbers:

ML42913

First Posted:

Jun 21, 2021

Last Update Posted:

Jul 18, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 18, 2022