The objective for this study is to evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in patients with untreated extensive-stage small cell lung cancer (ES-SCLC)…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Progression-free survival (PFS) after randomization, defined as the time from
randomization to the first occurrence of disease progression or death from any
cause (whichever occurs first), as determined by the investigator according to
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. (in the PAS)
-Overall survival (OS) after randomization, defined as the time from
randomization to death from any cause. (in the PAS)
Up to 50 months
Secondary outcome
-Confirmed objective response rate (ORR), defined as the proportion of patients
with a complete response (CR) or partial response (PR) on two consecutive
occasions => 4 weeks apart, as determined by the investigator according to
RECIST v1.1. (in the PAS and FAS)
-Duration of response (DOR) for patients with confirmed objective response,
defined as the time from the first occurrence of a documented objective
response to disease progression or death from any cause (whichever occurs
first), as determined by the investigator according to RECIST v1.1 (in the PAS
and FAS)
-PFS rates at 6 months and at 12 months (PAS and FAS)
-OS rates at 12 months and 24 months (PAS and FAS)
-Time to sustained deterioration (TTSD) in patient-reported physical
functioning and global health status, as measured by the European Organisation
for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire
Core (QLQ-C30)/ (PAS and FAS)
Up to 50 months
Background summary
The current standard first-line treatment for patients with ES-SCLC is
chemotherapie. Despite the survival benefit observed with this regimen, median
survival remains at approximately 8 months, leaving considerable room for
improvement in outcomes.
Tumor-cell killing by cytotoxic chemotherapy can reasonably be expected to
expose the immune system to high levels of tumor antigens. Therefore,
invigorating tumor-specific T-cell immunity by inhibiting PD-L1/PD-1 signaling
and TIGIT/PVR may result in deeper
and more durable responses compared with standard chemotherapy alone
Evaluating the safety and efficacy of these treatment combinations in patients
with SCLC will enable future tests of this hypothesis.
In light of these observations, this study (Study GO41767) is designed to
evaluate whether the anti-tumor effect of the combination of atezolizumab plus
CE (IMpower133 regimen) can be enhanced by adding tiragolumab in treating
patients with
chemotherapy-naive ES-SCLC.
Refer to section 1 of the protocol for a more elaborate background and study
rationale.
Study objective
The objective for this study is to evaluate the efficacy of tiragolumab plus
atezolizumab and carboplatin and etoposide (CE) compared with placebo plus
atezolizumab and CE in patients with untreated extensive-stage small cell lung
cancer (ES-SCLC) on the basis of progression free survival (PFS) and overall
survival (OS) in primary analysis set (PAS), patients without presence or
history of brain metastases at baseline.
Study design
This is a randomized, Phase III, global, multicenter, double-blinded,
placebo-controlled study designed to evaluate the safety and efficacy of
tiragolumab in combination with atezolizumab and CE compared with treatment
with placebo in combination with atezolizumab and CE in patients who have
ES-SCLC and are chemotherapy naive for their extensive-stage disease.
After screening, there are 3 phases in this study: induction, maintenance and
follow-up.
The study design is elaborately described in figure 1 and appendix 1 of the
protocol.
Intervention
Eligible patients will be randomized 1:1 to receive one of the following
treatment regimens during the induction phase
-Arm A: tiragolumab plus atezolizumab and CE
-Arm B: placebo plus atezolizumab and CE
Induction treatment will be administered on a 21-day cycle for 4 cycles.
Following the induction phase, patients will continue maintenance therapy with
either atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm
B).
Study burden and risks
The general burden on the patient consists, among other things, of blood
samples (every cycle), possible tumor biopsy, the use of the investigational
products (every cycle) with which various possible adverse effects are
associated.
Beneluxlaan 2A
Woerden 3446GR
NL
Beneluxlaan 2A
Woerden 3446GR
NL
Listed location countries
Age
Inclusion criteria
- Age > 18 years
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Histologically or cytologically confirmed ES-SCLC
- No prior systemic treatment for ES-SCLC
- For patients who have received prior chemoradiotherapy for limited-stage
SCLC: must have had treatment with curative intent and a treatment-free
interval of at least 6 months between the last dose/cycle of chemotherapy,
thoracic radiotherapy, or chemoradiotherapy and the diagnosis of ES-SCLC
- Measurable disease, as defined by Response Evaluation Criteria in Solid
Tumors version 1.1
- Submission of a pre-treatment tumor tissue sample
- Adequate hematologic and end-organ function
Exclusion criteria
- Symptomatic or actively progressing CNS metastases
- Spinal cord compression not definitively treated with surgery and/or
radiation, or previously diagnosed and treated spinal cord compression without
evidence that disease has been clinically stable for > 1 week prior to
randomization
- Leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring
recurrent drainage procedures, hypercalcemia
- Known clinically significant liver disease
- Malignancies other than SCLC within 5 years prior to randomization, with
the exception of those with a negligible risk of metastasis or death treated
with expected curative outcome
- Active or history of autoimmune disease or immune deficiency
- Treatment with any other investigational agent with therapeutic intent
within 28 days prior to randomization
- Pregnancy or breastfeeding, or intention of becoming pregnant during study
treatment or within 5 months after the final dose of atezolizumab or
tiragolumab or for 6 months after the final dose of carboplatin or etoposide.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-003301-97-NL |
| ClinicalTrials.gov | NCT04256421 |
| CCMO | NL72355.056.20 |