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)

Gastric Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04933227
• Other study ID #: ML42913
• Status: Terminated
• Phase: Phase 2
• Start date: August 6, 2021
• Est. completion date: November 17, 2023

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: November 17, 2023
• Est. primary completion date: November 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Stomach Neoplasms

Intervention

Drug:
• Atezolizumab
Atezolizumab 1200 mg will be administered intravenously (IV) on Day 1 of each 21-day cycle.
• Tiragolumab
Tiragolumab 600 mg will be administered IV on Day 1 of each 21-day cycle.
• Oxaliplatin
Oxaliplatin 130 mg/m^2 will be administered IV on Day 1 of each 21-day cycle during Cycles 1-4.
• Capecitabine
Capecitabine 1000 mg/m^2/d will be administered orally (PO) twice daily (bid) on Days 1-14 during Cycles 1-4.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	Hunan Cancer Hospital	Changsha CITY
China	Changzhou First People's Hospital	Changzhou
China	The First Affiliated Hospital of College of Medicine, Zhejiang University; Medical Oncology	Hangzhou
China	The First Affiliated Hospital of Anhui Medical University	Hefei
China	Anhui Province Cancer Hospital	Hefei City
China	Liaoning cancer Hospital & Institute	Shenyang
China	Tianjin Cancer Hospital	Tianjin
China	Hubei Cancer Hospital	Wuhan
China	The First Affiliated Hospital of Xiamen University	Xiamen

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) in the Full Analysis Set (FAS) Population		Up to approximately 20 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from Baseline in EORTC QLQ-C30 in the FAS Population		Up to approximately 20 months
Secondary	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
Secondary	Change from Baseline in EORTC QLQ-STO22 in the FAS Population		Up to approximately 20 months
Secondary	ORR in a Subgroup Population With PD-L1 and/or TIGIT Positive Expression		Up to approximately 20 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants With Adverse Events		Up to approximately 20 months