A Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Participants With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04832854

Collaborator

(none)

Enrollment

Locations

Arms

70.2

Anticipated Duration (Months)

3.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the surgical safety and feasibility of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment for participants with previously untreated locally advanced non-small cell lung cancer (NSCLC). The study will also evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by adjuvant atezolizumab plus tiragolumab or adjuvant platinum-based chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer (NSCLC)	Drug: Atezolizumab Drug: Tiragolumab Drug: Carboplatin Drug: Cisplatin Drug: Pemetrexed Drug: Gemcitabine Drug: Paclitaxel	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

82 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Patients With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer

Actual Study Start Date :

Apr 23, 2021

Anticipated Primary Completion Date :

Feb 28, 2027

Anticipated Study Completion Date :

Feb 28, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A (PD-L1 High) Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: cisplatin/carboplatin + pemetrexed (for non-squamous only) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel	Drug: Atezolizumab Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. Other Names: Tecentriq Drug: Tiragolumab Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle. Other Names: MTIG7192A Drug: Carboplatin Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Cisplatin Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Pemetrexed Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Gemcitabine Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle. Drug: Paclitaxel Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
Experimental: Cohort B (PD-L1 All Comers) All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: cisplatin/carboplatin + pemetrexed (for non-squamous only) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel	Drug: Atezolizumab Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. Other Names: Tecentriq Drug: Tiragolumab Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle. Other Names: MTIG7192A Drug: Carboplatin Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Cisplatin Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Pemetrexed Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Gemcitabine Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle. Drug: Paclitaxel Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Arm

Intervention/Treatment

Experimental: Cohort A (PD-L1 High)

Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: cisplatin/carboplatin + pemetrexed (for non-squamous only) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel

Drug: Atezolizumab

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

Other Names:

Tecentriq

Drug: Tiragolumab

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

Other Names:

MTIG7192A

Drug: Carboplatin

Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle.

Drug: Cisplatin

Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Drug: Pemetrexed

Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Drug: Gemcitabine

Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.

Drug: Paclitaxel

Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Experimental: Cohort B (PD-L1 All Comers)

All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: cisplatin/carboplatin + pemetrexed (for non-squamous only) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel

Drug: Atezolizumab

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

Other Names:

Tecentriq

Drug: Tiragolumab

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

Other Names:

MTIG7192A

Drug: Carboplatin

Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle.

Drug: Cisplatin

Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Drug: Pemetrexed

Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Drug: Gemcitabine

Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.

Drug: Paclitaxel

Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Outcome Measures

Primary Outcome Measures

Number of Participants With Surgical Delays [Up to approximately 6 years]
Number of Participants With Operative and Post-operative Complications [Up to approximately 6 years]
Number of Participants With Surgical Cancellations Related to Study Treatment [Up to approximately 6 years]
Percentage of Participants With Adverse Events [Up to approximately 6 years]
Percentage of Participants Who Achieve Major Pathological Response (MPR) [At the time of surgery (approximately Weeks 17-20)]

Secondary Outcome Measures

Percentage of Participants With Pathological Complete Response (pCR) [At the time of surgery (approximately Weeks 17-20)]
Event Free Survival (EFS) [From baseline to disease progression that precludes surgical resection, or local or distant disease recurrence after surgery, or death from any cause (up to approximately 6 years)]
Serum Concentrations of Atezolizumab [Day 1 of Cycle 1 (cycle=21 days): pre-dose and 30 minutes (min) post-dose; Day 1 of Cycles 2, 3, 4, 5, 8, 12, 16: pre-dose; at treatment discontinuation (TD) visit (up to approximately 9 months)]
Serum Concentrations of Tiragolumab [Day 1 of Cycle 1 (cycle=21 days): pre-dose and 30 min post-dose; Day 1 of Cycles 2, 3, 4, 5, 8, 12, 16: pre-dose; at TD visit (up to approximately 9 months)]
Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab [Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12 and 16 (cycle=21 days) and at TD visit (up to approximately 9 months)]
Percentage of Participants With ADAs to Tiragolumab [Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12 and 16 (cycle=21 days) and at TD visit (up to approximately 9 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key inclusion criteria:

Histologically or cytologically confirmed Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology
Eligible for R0 resection with curative intent at the time of screening
Adequate pulmonary function to be eligible for surgical resection with curative intent
Eligible to receive a platinum-based chemotherapy regimen
Measurable disease, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Availability of a representative tumor specimen that is suitable for determination of PD-L1 status
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Normal life expectancy, excluding lung cancer mortality risk
Adequate hematologic and end-organ function
Negative human immunodeficiency virus (HIV) test at screening
Negative serology for active hepatitis B virus (HBV) and active hepatitis C virus (HCV) at screening

Key Exclusion Criteria:

NSCLC with histology of large cell neuroendocrine carcinoma, sarcomatoid carcinoma, or NSCLC not otherwise specified
Small cell lung cancer (SCLC) histology or NSCLC with any component of SCLC
Any prior therapy for lung cancer
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Active tuberculosis
Significant cardiovascular disease
NSCLC with an activating EGFR mutation or ALK fusion oncogene
Known c-ros oncogene 1 (ROS1) rearrangement
History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with negligible risk of metastasis or death
Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
Prior treatment with CD127 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-TIGIT, and anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents
Treatment with systemic immunosuppressive medication
Pregnancy or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics	Duarte	California	United States	91010
2	University of Southern California	Los Angeles	California	United States	90033
3	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
4	Georgetown U; Lombardi Comp Can	Washington	District of Columbia	United States	20016-1468
5	Washington University School of Medicine; Medical Oncology	Saint Louis	Missouri	United States	63110
6	Winthrop Univ Hospital	Mineola	New York	United States	11501
7	NYU Cancer Center	New York	New York	United States	10016
8	Columbia University	New York	New York	United States	10032-3725
9	Kosin University Gospel Hospital	Busan		Korea, Republic of	49267
10	St. Vincent's Hospital	Gyeonggi-do		Korea, Republic of	16247
11	Seoul National University Hospital	Seoul		Korea, Republic of	03080
12	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
13	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona	Spain	8208
14	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña	Spain	15006
15	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid	Spain	28222
16	Vall d´Hebron Institute of Oncology (VHIO), Barcelona	Barcelona		Spain	08035
17	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
18	Kantonsspital Baden; Medizinische Klinik, Onkologie	Baden		Switzerland	5404
19	Universitaetsspital Basel; Onkologie	Basel		Switzerland	4031
20	Inselspital Bern; Universitätsklinik für medizinische Onkologie	Bern		Switzerland	3010
21	Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie	Chur		Switzerland	7000
22	Kantonsspital St. Gallen; Onkologie/Hämatologie	St. Gallen		Switzerland	9007
23	Kantonsspital Winterthur; Medizinische Onkologie	Winterthur		Switzerland	8401
24	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich		Switzerland	8091