Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (LuCa-MERIT-1)

• ClinicalTrials.gov Identifier: NCT05142189
• Recruitment Status: Recruiting
• First Posted: December 2, 2021
• Last Update Posted: April 16, 2024
• Sponsor: BioNTech SE
• Information provided by (Responsible Party): BioNTech SE

Tracking Information

• First Submitted Date: November 24, 2021
• First Posted Date: December 2, 2021
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: June 17, 2022
• Estimated Primary Completion Date: January 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 2023)

• Cohorts 1, 2, 3, 4, and 6: Occurrence of dose-limiting toxicities (DLTs) during Cycle 1 [ Time Frame: assessed during the first cycle (21 days) ]
• Cohorts 1 to 6: Occurrence of treatment-emergent adverse events (TEAEs) reported by relationship, seriousness, and grade according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 [ Time Frame: up to 27 months ]
• Cohort 6 only: Occurrence of post-surgical adverse events (AEs) related to BNT116 and cemiplimab [ Time Frame: up to 27 months ]
• Cohort 6 only: Occurrence of treatment-related delays to surgery more than 9 weeks post the last dose of neo-adjuvant treatment [ Time Frame: up to 6 months ]

Original Primary Outcome Measures (submitted: November 24, 2021)

• Occurrence of dose-limiting toxicities (DLTs) during Cycle 1 [ Time Frame: assessed during the first cycle (21 days) ]
• Occurrence of unsolicited treatment-emergent adverse events (TEAEs) reported by relationship, seriousness, and grade according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 [ Time Frame: up to 27 months ]

Current Secondary Outcome Measures (submitted: October 4, 2023)

• Cohorts 1 to 4: Overall response rate (ORR) defined as the number of patients with complete response (CR) or partial response (PR) as best overall response (BOR) [ Time Frame: up to 27 months ]
  according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of patients in the efficacy analysis set
• Cohorts 1 to 4: Duration of response (DoR) defined as the time from initial response until first objective tumor progression according to RECIST v1.1 [ Time Frame: up to 27 months ]
• Cohorts 1 to 4: Disease control rate (DCR) defined as the number of patients with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 divided by the number of patients in the efficacy analysis set [ Time Frame: up to 27 months ]
• Cohorts 1 to 4: Duration of disease control defined as the time from initial detection of stable disease or response until first objective tumor progression according to RECIST v1.1 [ Time Frame: up to 27 months ]
• Cohorts 1 to 4: Progression-free survival (PFS) defined as the time of first trial treatment until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first [ Time Frame: up to 48 months ]
• All cohorts: Overall survival (OS) defined as the time of first trial treatment until death from any cause [ Time Frame: up to 48 months ]
• Cohort 5 and 6: Event free survival (EFS) defined as the length of time from first trial treatment to any of the following events: progression of disease, recurrence of disease or death from any cause, whichever occurs first. [ Time Frame: up to 48 months ]
• Cohort 5 and 6: EFS rate at 12 and 24 months defined as the number of patients without an EFS-defining event divided by the number of patients in the efficacy analysis set. [ Time Frame: up to 24 months ]
• Cohort 6: Rate of pathologic responses defined as the number of patients with major or complete pathologic response in the surgical specimen from surgery after neo-adjuvant trial treatment divided by the number of patients in the efficacy analysis set. [ Time Frame: At time of surgery (approximately after 3 months treatment) ]
• Cohort 6: ORR at the end of neo-adjuvant treatment (using RECIST v1.1). [ Time Frame: Up to 3 months ]
• Cohort 6: Rate of progressive disease at the end of neo-adjuvant treatment (using RECIST v1.1). [ Time Frame: Up to 3 months ]

Original Secondary Outcome Measures (submitted: November 24, 2021)

• Overall response rate (ORR) defined as the number of patients with complete response (CR) or partial response (PR) as best overall response (BOR) [ Time Frame: up to 27 months ]
  according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of patients in the efficacy analysis set
• Duration of response (DoR) defined as the time from initial response until first objective tumor progression according to RECIST v1.1 [ Time Frame: up to 27 months ]
• Disease control rate (DCR) defined as the number of patients with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 divided by the number of patients in the efficacy analysis set [ Time Frame: up to 27 months ]
• Duration of disease control defined as the time from initial detection of stable disease or response until first objective tumor progression according to RECIST v1.1 [ Time Frame: up to 27 months ]
• Progression-free survival (PFS) defined as the time of first trial treatment until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first [ Time Frame: up to 48 months ]
• Overall survival (OS) defined as the time of first trial treatment until death from any cause [ Time Frame: up to 48 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer
• Official Title: LuCa-MERIT-1: First-in-human, Open Label, Phase I Dose Confirmation Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer
• Brief Summary: This First-in-human (FIH) trial for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination with cemiplimab or docetaxel in patients with advanced or metastasized non-small cell lung cancer (NSCLC) and unresectable NSCLC after chemoradiotherapy (CRT). Furthermore, the trial aims to establish the safety and feasibility of BNT116 in combination with cemiplimab and chemotherapy (carboplatin+paclitaxel) as neo-adjuvant treatment in resectable NSCLC followed by surgery and adjuvant BNT116 + cemiplimab. The trial will comprise several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Biological: BNT116
  intravenous injection
• Biological: Cemiplimab
  intravenous infusion
• Drug: Docetaxel
  intravenous infusion
• Drug: Carboplatin
  intravenous infusion
• Drug: Paclitaxel
  intravenous infusion

Study Arms

• Experimental: Cohort 1A - BNT116 monotherapy
  Intervention: Biological: BNT116
• Experimental: Cohort 1B - BNT116 monotherapy
  Intervention: Biological: BNT116
• Experimental: Cohort 2 - BNT116 + cemiplimab (PD-1/PD-L1 inhibitor refractory/relapsed patients)
  Interventions:

  • Biological: BNT116
  • Biological: Cemiplimab
• Experimental: Cohort 3 - BNT116 + docetaxel
  Interventions:

  • Biological: BNT116
  • Drug: Docetaxel
• Experimental: Cohort 4 - BNT116 + cemiplimab (frail patients)
  Interventions:

  • Biological: BNT116
  • Biological: Cemiplimab
• Experimental: Cohort 5 - BNT116 + cemiplimab (after concurrent chemoradiotherapy [CRT])
  Interventions:

  • Biological: BNT116
  • Biological: Cemiplimab
• Experimental: Cohort 6 - BNT116 + cemiplimab + carboplatin + paclitaxel
  BNT116 + cemiplimab + carboplatin + paclitaxel as neo-adjuvant treatment followed by surgery, thereafter adjuvant treatment with BNT116 + cemiplimab
  Interventions:

  • Biological: BNT116
  • Biological: Cemiplimab
  • Drug: Carboplatin
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 4, 2023): 130
• Original Estimated Enrollment (submitted: November 24, 2021): 80
• Estimated Study Completion Date: August 2027
• Estimated Primary Completion Date: January 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Patients must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Patients in Cohort 1 and Cohort 5 do not have to present with measurable disease.

  1. Patients in Cohorts 1 to 4 must present with unresectable Stage III or metastatic Stage IV NSCLC by American Joint Commission on Cancer (AJCC) Cancer Staging Manual, Eighth Edition.
  2. Patients in Cohort 5 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-trial chemoradiotherapy.
  3. Patients in Cohort 6 with the initial diagnosis of resectable Stage II and Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition.
• Patients in Cohorts 2, 4, 5, and 6 must be able to tolerate (additional) anti-PD-1 therapy (i.e., did not permanently discontinue anti-programmed death protein 1 [PD-1] / programmed death ligand 1 [PD-L1] therapy due to toxicity).
• Patients in Cohorts 2, 3, and 6 must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1. Patients in Cohort 1, 4, and 5 with an ECOG-PS of 0-2 are eligible.

Cohort-specific inclusion criteria:

Cohort 1:

• Patients' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen as well as one other line of systemic therapy (except if a patient is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor and/or another line of systemic therapy).

  • Note: Patients newly enrolled in Cohort 1B under clinical trial protocol v4.0 and subsequent versions of the clinical trial protocol must consent to mandatory blood sampling for peripheral blood mononuclear cells (PBMCs).
• Patients who are to start cemiplimab at Cycle 3 must present with PD-L1 expression of tumor proportion score (TPS) ≥1% in tumor cells (as determined locally).

Cohort 2:

• Patients must present with PD-L1 expression of tumor proportion score (TPS) ≥50% in tumor cells (as determined locally prior to inclusion in this trial).

• Patients must present with progressive disease either

  1. in the advanced or metastasized stage of NSCLC: while on a PD-1/PD-L1 inhibitor therapy or within 6 months of termination of this treatment as first-line treatment. Or
  2. be refractory to ongoing adjuvant therapy with a PD-1/PD-L1 inhibitor that has been given for at least 3 months in monotherapy (i.e., after an initial combination therapy) before being enrolled into this trial.

Cohort 3:

• Patients' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a patient is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).
• Patients must present with progressive disease.

Cohort 4:

• Patients' who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled if presenting with PD-L1 expression: TPS ≥1% in tumor cells (as determined locally).

Cohort 5:

• Patients' NSCLC must have been considered unresectable due to patients' condition and/or tumor-related factors and the patients must have undergone chemoradiotherapy before entering the trial.

Cohort 6:

• Patients' NSCLC must be considered technically and medically resectable.
• Patients must be considered eligible for neo-adjuvant treatment.

Key Exclusion Criteria:

• Ongoing active systemic treatment against NSCLC.
• Presence of a driver mutation for which approved target therapies are available except if the patient is not a candidate for the respective targeted therapy.
• Ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may suggest risk for immune-related adverse events. Note: Patients with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism who are in remission, or on a stable dose of thyroid-replacement hormone, vitiligo, or psoriasis may be included.
• Current evidence of new or growing brain or spinal metastases during screening. Patients with leptomeningeal disease are excluded. Patients with known brain or spinal metastases may be eligible in Cohorts 1 to 4 if they:
• had radiotherapy or another appropriate therapy for the brain or spinal bone metastases, AND
• have no neurological symptoms that can be attributed to the current brain lesions, AND
• have stable brain or spinal disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent (confirmed by stable lesions on two scans at least 4 weeks apart), AND
• do not require steroid therapy for the treatment of brain or spinal metastases within 14 d before the first dose of trial treatment. Note: Spinal bone metastases (i.e., of the vertebrae) are allowed, unless imminent fracture or cord compression is anticipated.
• Systemic immune suppression:

• Current use of chronic systemic steroid medication (≤5 mg/day prednisolone equivalent is allowed); patients using physiological replacement doses of prednisone for adrenal or pituitary insufficiency are eligible.

  • Note: Steroid medication given for supportive or prophylactic reasons during CRT for patients in Cohort 5 needs to be tapered to ≤5 mg/day prednisolone equivalent at latest on the day before the trial treatment starts.
• Other clinically relevant systemic immune suppression within the last 3 months before trial enrollment.
• Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+ T-cell (CD4+) counts <350 cells/µL and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
• Prior splenectomy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BioNTech clinical trials patient information; +49 6131 9084 ext 0; patients@biontech.de

• Listed Location Countries: Germany, Hungary, Poland, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05142189
• Other Study ID Numbers: BNT116-01; 2021-004739-94 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioNTech SE
• Original Responsible Party: Same as current
• Current Study Sponsor: BioNTech SE
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

• PRS Account: BioNTech SE
• Verification Date: April 2024