Safety and Effectiveness of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer

Registration Number
NCT06712355
Lead Sponsor
BioNTech SE
Brief Summary

This is a Phase III, multisite, randomized, double-blinded study to investigate 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

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, trial 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).
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Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
439
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 or immunotherapy 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 systemic anticancer treatment including chemotherapy, radiotherapy, immunotherapy, 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.

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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 trial treatment:

    • Within 2 weeks: small molecule agents with half-life of <7 days; radiation not involving the thoracic cavity; local radiation for brain lesions is allowed; local radiation for bone lesions is allowed.
    • 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 a programmed death (ligand)-1 (PD[L]-1)/vascular endothelial growth factor (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 10 days prior to the initiation of trial 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 within 10 days before initiating IMP of this trial.
    • Participants with known leptomeningeal metastases.
  • Have serious non-healing wound, ulcer, or 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 trial 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 evidence of major coagulation disorders or other significant risks of hemorrhage such as:

    • History of intracranial or intraspinal hemorrhage.
    • Tumor lesions invading large vessels and with significant risk of bleeding.
    • Had clinically significant hemoptysis or tumor hemorrhage within 1 month prior to the trial treatment.
  • Have superior vena cava syndrome or symptoms of spinal cord compression.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1 - Atezolizumab + Etoposide + CarboplatinAtezolizumab-
Arm 1 - Atezolizumab + Etoposide + CarboplatinEtoposide-
Arm 1 - Atezolizumab + Etoposide + CarboplatinCarboplatin-
Arm 2 - BNT327 Dose 1 + Etoposide + CarboplatinBNT327-
Arm 2 - BNT327 Dose 1 + Etoposide + CarboplatinEtoposide-
Arm 2 - BNT327 Dose 1 + Etoposide + CarboplatinCarboplatin-
Arm 3 - BNT327 Dose 2 + Etoposide + CarboplatinBNT327-
Arm 3 - BNT327 Dose 2 + Etoposide + CarboplatinEtoposide-
Arm 3 - BNT327 Dose 2 + Etoposide + CarboplatinCarboplatin-
Primary Outcome Measures
NameTimeMethod
Overall survival (OS)Up to approximately 39 months

OS defined as the time from randomization to death from any cause.

Secondary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)Up to approximately 39 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.

Objective response rate (ORR)Up to approximately 39 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.

PFS rate based on investigator's assessmentAt 6, 12, and 18 months
OS rateAt 6, 12, 18, and 24 months
Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationshipFrom the first dose of IMP to the 90-Day Follow-up Visit

TEAEs graded according to (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)

Occurrence of dose delay, infusion interruption and discontinuation of investigational medicinal product (IMP) due to TEAEs (including related TEAEs)From first to last IMP dose, 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 39 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 functioningUp to approximately 39 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 39 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-LC29Up to approximately 39 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-LC29Up to approximately 39 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.

Change from baseline in fatigue domain score scale of the NSCLC-SAQUp to approximately 39 months

NSCLC-SAQ consists of seven items assessing 5 NSCLC symptom concepts: cough, pain, dyspnea, fatigue, and poor appetite. All items have a recall period of past 7 days and a 5-point response scale ranging from 0: "No symptom at all" to 4: "Very severe symptom" or from 0: "Never" to 4: "Always" to measure attributes of symptom intensity or frequency, respective...

Change from baseline in pain domain score of the Non-Small-Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)Up to approximately 39 months

NSCLC-SAQ consists of seven items assessing 5 NSCLC symptom concepts: cough, pain, dyspnea, fatigue, and poor appetite. All items have a recall period of past 7 days and a 5-point response scale ranging from 0: "No symptom at all" to 4: "Very severe symptom" or from 0: "Never" to 4: "Always" to measure attributes of symptom intensity or frequency, respective...

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