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
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Non-Small Cell Lung Cancer (NSCLC)
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 50
- Locations
- 21
- Primary Endpoint
- Number of Participants With Surgical Delays
- Status
- Terminated
- Last Updated
- last month
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Atezolizumab
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Tiragolumab
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Carboplatin
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Cisplatin
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Atezolizumab
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Pemetrexed
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Gemcitabine
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Paclitaxel
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Tiragolumab
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Carboplatin
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Cisplatin
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Pemetrexed
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Gemcitabine
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) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Number of Participants With Surgical Delays
Time Frame: Up to approximately 4.7 months
Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the electronic case report forms (eCRFs).
Number of Participants With Operative and Post-operative Complications
Time Frame: From day of surgery up to end of safety follow-up (up to approximately 17.5 months)
Participants who underwent surgical resection of their tumor and had intraoperative or post-operative complications were reported.
Number of Participants With Surgical Cancellations Related to Study Treatment
Time Frame: Up to approximately 4.7 months
Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant for to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the eCRFs.
Number of Participants With Adverse Events (AEs)
Time Frame: From signing of informed consent to up to 90 days after the final dose of study treatment (Up to approximately 1.7 years)
AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; Any new disease or exacerbation of an existing disease; Recurrence of an intermittent medical condition not present at baseline; Any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study treatment; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Major Pathological Response (MPR) Rate
Time Frame: At the time of surgical resection (From Day 114 to Day 144)
MPR rate was defined as the percentage of participants who achieved MPR. MPR was defined as ≤10% residual viable tumor at the time of surgical resection in the primary tumor, as assessed by the local pathology laboratory. Patients who did not proceed to surgery were considered as non-responders for MPR. 95% confidence interval (CI) was calculated using the Wilson Score Method. Percentages have been rounded off.
Secondary Outcomes
- Serum Concentrations of Tiragolumab at Specified Timepoints(Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, 16; 30 minutes (min) post-infusion Cycle 1 Day 1; (Cycle=21 days))
- Percentage of Participants With Pathological Complete Response (pCR)(At the time of surgical resection (From Day 114 to Day 144))
- Event-free Survival (EFS)(Up to approximately 3.8 years)
- Serum Concentrations of Atezolizumab at Specified Timepoints(Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, and 16; 30 minutes (min) post-infusion Day 1 of Cycle 1; (Cycle=21 days))
- Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab(Up to approximately 3.8 years)
- Percentage of Participants With ADAs to Tiragolumab(Up to approximately 3.8 years)