Extensive-stage Small-cell Lung Cancer
Conditions
Keywords
First-line ES-SCLC, SCLC, Immunotherapy in combination with chemotherapy, Untreated, Bispecific antibody, Programmed death-ligand 1 (PD-L1), Vascular endothelial growth factor (VEGF) A, Immunotherapy, Combination with other investigational agents, Pumitamig, BNT327, Check point inhibitor, Lung cancer, Etoposide, Carboplatin, Cisplatin
Brief summary
This is a Phase III, multisite, randomized, double-blinded study to investigate pumitamig (BNT327) combined with chemotherapy (etoposide/carboplatin) compared to atezolizumab combined with chemotherapy (etoposide/carboplatin) for the treatment of participants with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).
Detailed description
There are two stages in this study: Stage 1 will have two treatment arms and one control arm, and Stage 2 will have a treatment arm and a control arm. The control arms in Stages 1 and 2 are the same. Each stage of the study consists of a screening period (up to 21 days), an induction period followed by a maintenance period (until confirmed disease progression, intolerable toxicity, participant withdrawal, study termination or up to 2 years \[whichever occurs first\]), and a follow-up (FU) period for all participants (2 safety FU visits and survival FU visits). In Stage 1, eligible participants will be randomized (1:1:1) to the arms. In Stage 2, participants will then be randomized (1:1) to the arms. The randomization will be stratified based on the following factors: 1. Brain or liver metastases per investigator assessment (presence versus absence); 2. Smoking status (smoker versus never-smoker); and 3. Geography. Participants will be allowed to switch to cisplatin if carboplatin is not tolerated at the investigator's discretion.
Interventions
DRUGPumitamig
Intravenous infusion
DRUGAtezolizumab
Intravenous infusion
DRUGEtoposide
Intravenous infusion and capsules
DRUGCarboplatin (or cisplatin if carboplatin is not tolerated)
Intravenous infusion
Sponsors
BioNTech SE
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically or cytologically confirmed ES-SCLC (using the AJCC \[American Joint Committee on Cancer\] tumor node metastasis staging system combined with Veterans Administration Lung Study Group \[VALG\]'s two stage classification scheme). For AJCC tumor node metastasis staging system: AJCC 8th edition stage IV (T any, N any, M1a/b/c), or T3\~4 for multiple lung nodules or tumor/nodule volume that cannot be encompassed in a tolerable radiotherapy plan. * Have not had prior systemic therapy for ES-SCLC. However, participants with prior chemoradiotherapy for limited-stage-SCLC must have been treated with curative intent and had a treatment-free interval of at least 6 months after the last chemotherapy, radiotherapy, or chemoradiotherapy before diagnosis of ES-SCLC to be eligible. * Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate hematologic and organ function as defined in the protocol.
Exclusion criteria
* Have histologically or cytologically confirmed SCLC with combined histologies. * Have received any of the following therapies or drugs within the noted time intervals prior to study treatment: * Within 2 weeks: small molecule agents with half-life of \<7 days; radiation outside the thoracic cavity including whole brain radiation. Of note, other local radiation for brain lesions (not whole brain) is allowed; local radiation for bone lesions is allowed. Palliative bone radiation or brain stereotactic radiosurgery would not require a washout period, but participants should recover from radiotherapy-related toxicity. * Within 4 weeks: radiation involving the thoracic cavity; small molecule targeted agents with half-life of ≥7 days; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies. * Have received prior treatment with anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or programmed death (ligand)-1 (PD\[L\]-1)/VEGF bispecific antibody. * Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of study treatment. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) are allowed. * Have the following central nervous system metastases: * Participants with untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm). * Participants with treated central nervous system (CNS) metastases who are not neurologically stable or on steroids (at a dosage greater than 10 mg/Day of prednisone or an equivalent dose of other corticosteroid) within 7 days before initiating study treatment of this study. * Participants with known leptomeningeal metastases. * Have uncontrolled hypertension or poorly controlled diabetes prior to study treatment. * Have a serious or non-healing wound, or (incompletely healed) bone fracture. This includes history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before study entry. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation. * Have a significant risk of hemorrhage (per investigator clinical judgment) as defined in the protocol. * Have superior vena cava syndrome or symptoms of spinal cord compression that requires urgent medical intervention. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to approximately 46 months | OS defined as the time from randomization to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to approximately 46 months | ORR defined as the proportion of participants in whom a complete response (CR) or partial response (PR) (based on investigator's assessment per RECIST v1.1) is observed as best overall response with confirmation. |
| Duration of response (DOR) | Up to approximately 46 months | DOR defined as the time from onset of objective response (confirmed CR or PR based on investigator's assessment per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first. |
| PFS rate based on investigator's assessment | At 6, 12, and 18 months | — |
| OS rate | At 6, 12, 18, and 24 months | — |
| Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship | From the first dose of study treatment to the 90-Day Follow-up Visit | TEAEs graded according to (US) National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 |
| Occurrence of dose delay, infusion interruption and discontinuation of study treatment due to TEAEs (including related TEAEs) | From first to last dose of study treatment, i.e., up to 2 years | — |
| Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Core 30 questionnaire (QLQ-C30) Global Health status/Quality-of-Life score (Items 29 and 30) | Up to approximately 46 months | Global health status/QoL scale ranges in score from 0 to 100 with a high scale score representing a higher response level (e.g., high score for global health status/QoL is high QoL: high score for symptom scale/item is high symptomatology or problems). |
| Change from baseline in EORTC QLQ-C30 physical functioning | Up to approximately 46 months | Physical functioning scale ranges in score from 0 to 100 with a high scale score representing a higher response level (e.g., high score for functional scale is high/healthy level of functioning). |
| Change from baseline in coughing scale of the EORTC Quality-of-Life-Lung cancer 29 questionnaire (QLQ-LC29) | Up to approximately 46 months | Multi-item coughing scale ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems. |
| Change from baseline in shortness of breath scale of the EORTC QLQ-LC29 | Up to approximately 46 months | Multi-item shortness of breath scale ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems. |
| Change from baseline in coughed up blood item of the EORTC QLQ-LC29 | Up to approximately 46 months | Single item coughing up blood ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems. |
| Progression-free survival (PFS) | Up to approximately 46 months | PFS defined as the time from randomization to first objective tumor progression (progressive disease per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]), or death from any cause, whichever occurs first. |
| Change from baseline in Functional Assessment of Cancer Therapy-General overall bother item (FACT-GP5). | Up to approximately 46 months | The FACT-G - Item GP5 (Version 4) is a single-item summary measure of the overall impact of treatment toxicity, based upon its association with the number and degree of AEs in clinical studies, rated on a 5-point Likert scale ("not at all" to "very much") with a recall period of past 7 days. A high score represents high level of problems. |
Countries
Australia, China, Germany, Japan, Poland, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBioNTech clinical trials patient information
STUDY_DIRECTORBioNTech Responsible Person
BioNTech SE
Outcome results
None listed