A Study of Atezolizumab With or Without Tiragolumab Consolidation in Limited Stage Small Cell Lung Cancer

Roche

Status and phase: Terminated; Phase 2

Conditions: Carcinoma, Small Cell Lung

Treatments: Other: Placebo; Drug: Atezolizumab; Drug: Tiragolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04308785

ML41257

Details and patient eligibility

About

This is a multicenter, double-blind, placebo-controlled, randomized, phase II study to investigate the efficacy and safety of Atezolizumab with or without Tiragolumab as consolidation therapy in participants with limited stage small cell lung cancer who have not progressed during/after chemoradiotherapy.

Full description

Participants can receive concurrent or sequential chemoradiotherapy (CRT) as per local standard of care, but they must be randomized within 6 weeks from completion of chemoradiotherapy. Participants should receive 4 cycles of chemotherapy and radiotherapy dose of 56-64 Gy (once daily) before randomization, and those participants who have not progressed during/after CRT will be stratified by response to CRT, radiotherapy timing, and be randomized in a 1:1 ratio to Atezolizumab+Tiragolumab arm or Atezolizumab+placebo arm.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed Informed Consent Form
• ECOG performance status of 0 or 1
• Histologically confirmed limited-stage SCLC.
• Patients who have not progressed during/after chemoradiotherapy.
• Concurrent or sequential chemoradiotherapy per local clinical practice must have been completed within 6 weeks prior to the first study treatment. If concurrent CRT is used, at least two cycles of chemotherapy should have been conducted during radiotherapy. If sequential radiotherapy is used, induction chemotherapy should be given 2 cycles of chemotherapy before thoracic radiotherapy.
• Adequate hematologic and end organ function.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the final dose of atezolizumab or placebo, and 90 days after the final dose of tiragolumab or placebo, and 6 months for chemotherapy after the last dose of chemotherapy treatment, whichever is later.
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm.
• Patients must have recovered from all acute toxicities from previous therapy, excluding alopecia and toxicities related to prior therapy.
• Patients must submit a pre-treatment tumor tissue sample.

Exclusion criteria

• Histology mixtured or Extensive-stage SCLC (per the Veterans Administration Lung Study Group (VALG) staging system).
• Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease
• Malignancies other than SCLC within 5 years prior to study treatment initiation, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab and 90 days after the final dose of tiragolumab, and 6 months for chemotherapy after the final dose of the chemotherapy treatment.
• Active or history of autoimmune disease or immune deficiency
• Uncontrolled or symptomatic hypercalcemia
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Positive test result for HIV
• Patients with active hepatitis B or hepatitis C virus
• Active tuberculosis
• Severe infections within 4 weeks prior to study treatment initiation, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Significant cardiovascular disease
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA4, anti-tigit, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Unresolved toxic effects of grade 2 or higher (CTCAE 5.0), including grade ≥ 2 pneumonitis from previous therapy
• Active EBV infection or known or suspected chronic active EBV infection at screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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24 participants in 2 patient groups

Arm A: Atezolizumab + Tiragolumab

Experimental group

Description:

Participants will receive atezolizumab + tiragolumab intravenously on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and tiragolumab treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Arm B: Atezolizumab + Placebo

Experimental group

Description:

Participants will receive atezolizumab + placebo on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and placebo treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Other: Placebo

Drug: Atezolizumab