Non-Small Cell Lung Cancer
Conditions
Keywords
Cancer Vaccine, Non-Small Cell Lung Cancer, Combination with chemotherapy, Combination with other investigational agents, anti-B7-H3 antibody conjugated to topoisomerase I inhibitor, anti-HER3 antibody conjugated to topoisomerase I inhibitor, Immunotherapy, Antibody-drug conjugate (ADC), Anaplastic lymphoma kinase (ALK) rearranged Non-Small Cell Lung Cancer, Rearranged during transfection (RET) rearranged Non-Small Cell Lung Cancer, NSCLC, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, Epidermal growth factor receptor (EGFR)-mutant Non-Small Cell Lung Cancer, Combination with a programmed cell death protein 1 (PD-1) inhibitor, Human epidermal growth factor receptor 3
Brief summary
This first-in-human (FIH) study for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination with approved medicinal products and/or in combination with investigational medicinal products (IMPs) including, but not limited to, cemiplimab, docetaxel, carboplatin, paclitaxel, osimertinib, anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), rearranged during transfection (RET) TKIs, BNT316 (an anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\] antibody), an anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor, an anti-human epidermal growth factor receptor 3 (HER3) antibody conjugated to a topoisomerase I inhibitor or a bispecific antibody for programmed death ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A) in participants with non-small cell lung cancer (NSCLC). The study will comprise several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above. The study will enroll participants with NSCLC in advanced or metastatic stage in Cohorts 1 to 4 and Cohorts 7 to 10, unresectable NSCLC Stage III in Cohorts 5 and 11, resectable NSCLC of Stage II and III in Cohort 6, advanced/metastatic epidermal growth factor receptor (EGFR)-mutant NSCLC in Cohort EGFR, and advanced/metastatic ALK rearranged or RET rearranged NSCLC in Cohort ALK/RET. Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.
Detailed description
The maximum duration of treatment for each individual participant in this study is: * Cohorts 1 to 4, Cohorts 7 to 10, Cohort EGFR, and Cohort ALK/RET: 24 months. * Cohorts 5 and 11: 18 cycles, i.e., 12 months. * Cohort 6: 4 cycles of neo-adjuvant treatment and 18 cycles of adjuvant treatment, i.e., 12 months of adjuvant treatment.
Interventions
BIOLOGICALBNT116
Intravenous injection
BIOLOGICALCemiplimab
Intravenous infusion
DRUGDocetaxel
Intravenous infusion
DRUGCarboplatin
Intravenous infusion
DRUGPaclitaxel
Intravenous infusion
BIOLOGICALBNT316
Intravenous infusion
BIOLOGICALanti-B7-H3 antibody conjugated to topoisomerase I inhibitor
Intravenous infusion
BIOLOGICALanti-HER3 antibody conjugated to topoisomerase I inhibitor
Intravenous infusion
BIOLOGICALBispecific antibody for PD-L1 and VEGF-A
Intravenous infusion
BIOLOGICALOsimertinib
Oral
BIOLOGICALALK-inhibitor or RET-inhibitor
Oral
Sponsors
BioNTech SE
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Participants in Cohorts 1, 5 and 11 as well as in Cohorts EGFR and ALK/RET do not have to present with measurable disease. 1. Participants must present with unresectable Stage III or metastatic Stage IV NSCLC by American Joint Commission on Cancer (AJCC) Cancer Staging Manual, Eighth Edition. EXCEPT 2. Participants in Cohorts 5 and 11 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-study chemoradiotherapy. 3. Participants in Cohort 6 with the initial diagnosis of resectable Stage II and Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition. * Participants in Cohorts 2, 4, 5, 6, 10 and 11 must be able to tolerate (additional) anti-PD-1 therapy (i.e., did not permanently discontinue anti-programmed death protein 1 \[PD-1\] / PD-L1\] therapy due to toxicity). * Participants must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) less than or equal to (\<=) 1, except for participants in Cohorts 1, 4, 5, 10 and 11 who are eligible with an ECOG-PS of 0-2. Cohort-specific inclusion criteria: Cohort 1: * Participants' 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 participant is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor and/or another line of systemic therapy). Note: Participants newly enrolled in Cohort 1B under protocol v 5.0 and subsequent versions of the protocol must consent to mandatory blood sampling for peripheral blood mononuclear cells (PBMCs). * Participants who are to start cemiplimab at Cycle 3 must present with PD-L1 expression of tumor proportion score (TPS) greater than or equal to (\>=) 1% in tumor cells (as determined locally). Cohort 2: * Participants must present with PD-L1 expression of TPS \>= 50% in tumor cells (as determined locally prior to inclusion in this study). * Participants 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/maintenance treatment after CRT 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 study. Cohort 3: * Participants' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor). * Participants must present with progressive disease. Cohort 4: * Participants 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: * Participants' NSCLC must have been considered unresectable due to participant's condition and/or tumor-related factors and the participants must have undergone chemoradiotherapy before entering the study. Cohort 6: * Participants' NSCLC must be considered technically and medically resectable. * Participants must be considered eligible for neo-adjuvant treatment. Cohort 7: * Participants' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor). Note 1: Participants may have received prior therapy targeting CTLA-4, lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif \[ITIM\] domain (TIGIT), VEGF or VEGF receptor (VEGFR) inhibitor as monotherapy or part of a combination therapy. Note 2: If the participants' prior therapies included a CTLA-4 inhibitor, the participant must be able to tolerate (additional) treatment with the CTLA-4 inhibitor. * Participants must present with progressive disease at study enrollment. * Participants must consent to mandatory blood sampling for PBMCs. Cohorts 8 \& 9: * Participants' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor). * Participants must present with progressive disease at study enrollment. Cohort 10: * Participants who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled. Cohort 11: * Participants' NSCLC must have been considered unresectable due to participants condition and/or tumor related factors and the participants must have undergone chemoradiotherapy before entering the study. Cohort EGFR (will enroll only at selected sites in the US): * Participants' NSCLC must have classical EGFR mutations, i.e., ex19Del or L858R. * Participants must have ongoing treatment with osimertinib. Cohort ALK/RET (will enroll only at selected sites in the US): * Participants' NSCLC must have ALK rearrangement or RET rearrangement. * Participants must have ongoing treatment with a standard of care ALK TKI or RET TKI. Key
Exclusion criteria
* Ongoing active systemic treatment against NSCLC. * Presence of a driver mutation for which approved target therapies are available except if the participant is not a candidate for the respective targeted therapy. EXCEPT participants in Cohort EGFR and Cohort ALK/RET. * 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: Participants 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. Participants with leptomeningeal disease are excluded. Participants with known brain or spinal metastases may be eligible for all Cohorts, except for Cohorts 5, 6 and 11, if they: * had radiotherapy or another appropriate therapy for the brain or spinal 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 days before the first dose of study treatment. Note: Spinal bone metastases (that is, 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); participants 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 participants in Cohorts 5 and 11 needs to be tapered to \<= 5 mg/day prednisolone equivalent at latest on the day before the study treatment starts. * Other clinically relevant systemic immune suppression within the last 3 months before study enrollment. * Known history of seropositivity for human immunodeficiency virus (HIV) with cluster of differentiation 4 (CD4)+ T-cell (CD4+) counts less than (\<) 350 cells/microlitre (mcL) and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections. * Prior splenectomy. * History/risk of interstitial lung disease or low baseline lung function (baseline pulse oximetry of less than 92% oxygen saturation without additional oxygen). NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, EGFR and ALK/RET: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period | From first dose of IMP up to 21 days | Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US. |
| Cohorts 1 to 11, EGFR and ALK/RET: Occurrence of Treatment-Emergent Adverse Events (TEAEs) Reported by Relationship, Seriousness, and Grade | up to 27 months | According to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US. |
| Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab | 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 | up to 6 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR) | up to 27 months | ORR defined as the number of participants with complete response (CR) or partial response (PR) as best overall response (BOR) according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of participants in the efficacy analysis set. |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR) | up to 27 months | DoR defined as the time from initial response until first objective tumor progression according to RECIST v1.1. |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR) | up to 27 months | DCR defined as the number of participants with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set. |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control | 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. |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS) | up to 48 months | PFS defined as the time of first study treatment until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. |
| Cohorts EGFR (osimertinib): PFS | up to 48 months | Defined as the time of first treatment with osimertinib until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort EGFR will enroll only at selected sites in the US. |
| Cohort ALK/RET (ALK TKI or RET TKI): PFS | up to 48 months | Defined as the time of first treatment with a ALK TKI or RET TKI until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort ALK/RET will enroll only at selected sites in the US. |
| Cohorts EGFR and ALK/RET: (BNT116): PFS per molecular NSCLC subtype | up to 48 months | Defined as the time of first treatment with BNT116 until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US. |
| Cohorts 1-11: Overall Survival (OS) | up to 48 months | OS defined as the time of first study treatment until death from any cause. |
| Cohorts 5, 6 and 11: Event Free Survival (EFS) | up to 48 months | EFS defined as the length of time from first study treatment to any of the following events: progression of disease, recurrence of disease or death from any cause, whichever occurs first. |
| Cohort 6: Rate of Pathologic Responses | At time of surgery (approximately after 3 months treatment) | Rate of pathologic responses defined as the number of participants with major or complete pathologic response in the surgical specimen from surgery after neo-adjuvant study treatment divided by the number of participants in the efficacy analysis set. |
| Cohorts 5, 6 and 11: EFS Rate at 12 and 24 months | up to 24 months | EFS rate defined as the number of participants without an EFS-defining event divided by the number of participants in the efficacy analysis set. |
| Cohort 6: ORR at the End of Neo-Adjuvant Treatment (Using RECIST v1.1) | up to 3 months | ORR defined as the number of participants with CR or PR as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set. |
| Cohort 6: Rate of Progressive Disease at the End of Neo-Adjuvant Treatment (Using RECIST v1.1) | up to 3 months | — |
Countries
Australia, Germany, Hungary, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBioNTech clinical trials patient information
STUDY_DIRECTORBioNTech Responsible Person
BioNTech SE
Outcome results
None listed