Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer
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 approved medicinal products and/or in combination with investigational medicinal products (IMPs) including, but not limited to, cemiplimab, docetaxel, carboplatin, paclitaxel, 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 trial will comprise of several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above. The trial 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, and resectable NSCLC of Stage II and III in Cohort 6.
Study details:
The maximum duration of treatment for each individual participant in this trial is:. * Cohorts 1 to 4, and Cohorts 7 to 10: 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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Participants must have histologically confirmed NSCLC and measurable disease by RECIST v1.1.
- Participants must present with unresectable Stage III or metastatic Stage IV 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.
- Participants must have an 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.
- 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 for Cohort 1.
- Participants must present with PD-L1 expression of TPS >= 50% for Cohort 2.
- Participants prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen for Cohort 3.
- Participants who are not candidates for chemotherapy may be enrolled if presenting with PD-L1 expression: TPS >= 1% for Cohort 4.
- Participants NSCLC must have been considered unresectable due to participant's condition and/or tumor-related factors and undergone chemoradiotherapy for Cohort 5.
- Participants NSCLC must be considered technically and medically resectable for Cohort 6.
- Participants must present with progressive disease and prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen for Cohort 7.
- Participants must present with progressive disease for Cohorts 8 & 9.
- Participants who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled for Cohort 10.
- Participant's NSCLC must have been considered unresectable due to participant's condition and/or tumor-related factors and undergone chemoradiotherapy for Cohort 11.
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.
- Ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
- Current evidence of new or growing brain or spinal metastases during screening.
- Current use of chronic systemic steroid medication (<= 5 mg/day prednisolone equivalent is allowed).
- Other clinically relevant systemic immune suppression within the last 3 months before trial enrollment.
- Known history of seropositivity for HIV with CD4+ T-cell counts less than (<) 350 cells/microlitre and with a history of AIDS-defining opportunistic infections.
- Prior splenectomy.
- History/risk of interstitial lung disease or low baseline lung function.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1
Study ID
NCT05142189
Intervention or treatment
BIOLOGICAL: BNT116
BIOLOGICAL: Cemiplimab
DRUG: Docetaxel
DRUG: Carboplatin
DRUG: Paclitaxel
BIOLOGICAL: BNT316
BIOLOGICAL: anti-B7-H3 antibody conjugated to topoisomerase I inhibitor
BIOLOGICAL: anti-HER3 antibody conjugated to topoisomerase I inhibitor
BIOLOGICAL: Bispecific antibody for PD-L1 and VEGF-A
Conditions
- Non-Small Cell Lung Cancer
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Scientia Clinical Research
Select from list below to view details:
Scientia Clinical Research
Randwick, New South Wales, Australia
Royal North Shore Hospital
Sydney, New South Wales, Australia
Cancer Research SA
Adelaide, South Australia, Australia
Monash Health
Clayton, Victoria, Australia
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Who is running the clinical trial?
BioNTech SE
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Cohort 1A - BNT116 Monotherapy
| Biological: BNT116 |
EXPERIMENTAL: Cohort 1B - BNT116 Monotherapy
| Biological: BNT116 |
EXPERIMENTAL: Cohort 2 - BNT116 + Cemiplimab (PD-1/PD-L1 Inhibitor Refractory/Relapsed Participants)
| Biological: BNT116, Biological: Cemiplimab |
EXPERIMENTAL: Cohort 3 - BNT116 + Docetaxel
| Biological: BNT116, Drug: Docetaxel |
EXPERIMENTAL: Cohort 4 - BNT116 + Cemiplimab (Frail Participants)
| Biological: BNT116, Biological: Cemiplimab |
EXPERIMENTAL: Cohort 5 - BNT116 + Cemiplimab (After Concurrent Chemoradiotherapy [CRT])
| Biological: BNT116, Biological: Cemiplimab |
EXPERIMENTAL: Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel
| Biological: BNT116, Biological: Cemiplimab, Drug: Carboplatin, Drug: Paclitaxel |
EXPERIMENTAL: Cohort 7 - BNT116 + BNT316
| Biological: BNT116, Biological: BNT316 |
EXPERIMENTAL: Cohort 8: BNT116 + Anti-B7-H3 Antibody Conjugated to Topoisomerase I Inhibitor
| Biological: BNT116, Biological: anti-B7-H3 antibody conjugated to topoisomerase I inhibitor |
EXPERIMENTAL: Cohort 9: BNT116 + Anti-HER3 Antibody Conjugated to Topoisomerase I Inhibitor
| Biological: BNT116, Biological: anti-HER3 antibody conjugated to topoisomerase I inhibitor |
EXPERIMENTAL: Cohort 10: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (Frail Participants)
| Biological: BNT116, Biological: Bispecific antibody for PD-L1 and VEGF-A |
EXPERIMENTAL: Cohort 11: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (After Concurrent CRT)
| Biological: BNT116, Biological: Bispecific antibody for PD-L1 and VEGF-A |
EXPERIMENTAL: Cohort EGFR : BNT116 + osimertinib
| Biological: BNT116, Biological: Osimertinib |
EXPERIMENTAL: Cohort ALK/RET: BNT116 + ALK TKI or RET TKI
| Biological: BNT116, Biological: ALK-inhibitor or RET-inhibitor |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Cohorts 1, 2, 3, 4, 6, 7, 8, 9, 10 and 11: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period | Not Specified | From first dose of IMP up to 21 days |
| Cohorts 1 to 11: 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 | up to 27 months |
| Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab | Not Specified | 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 | Not Specified | up to 6 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR) | 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 patients in the efficacy analysis set. | up to 27 months |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR) | DoR defined as the time from initial response until first objective tumor progression according to RECIST v1.1. | up to 27 months |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR) | 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 patients in the efficacy analysis set. | up to 27 months |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control | 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. | up to 27 months |
| Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS) | 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. | up to 48 months |
| All cohorts: Overall Survival (OS) | OS defined as the time of first trial treatment until death from any cause. | up to 48 months |
| Cohort 5, 6 and 11: Event Free Survival (EFS) | 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. | up to 48 months |
| Cohort 5, 6 and 11: EFS Rate at 12 and 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. | up to 24 months |
| Cohort 6: Rate of Pathologic Responses | 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 trial treatment divided by the number of participants in the efficacy analysis set. | At time of surgery (approximately after 3 months treatment) |
| Cohort 6: ORR at the End of Neo-Adjuvant Treatment (Using RECIST v1.1) | ORR defined as the number of participants with CR or PR as BOR according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of patients in the efficacy analysis set. | Up to 3 months |
| Cohort 6: Rate of Progressive Disease at the End of Neo-Adjuvant Treatment (Using RECIST v1.1) | Not Specified | Up to 3 months |
References
Clinical Trials Gov: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung CancerOther trials to consider
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