A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC)

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBioNTech SE

About this trial

This is a multi-site, open-label, dose-finding study, consisting of Parts 1, 2a, and 2b to investigate the combination of BNT326 with BNT327 in participants with relapsed, progressive as well as treatment-naïve, advanced/metastatic non-small cell lung cancer (NSCLC).

This study will enroll adult participants with histologically or cytologically confirmed NSCLC that is advanced (i.e., either metastatic or recurrent tumors with no known curative treatment available).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged ≥18 years at the time of giving informed consent.

Have measurable disease defined by RECIST v1.1.

All participants have to provide a tumor tissue sample (e.g. Formalin-fixed paraffin-embedded [FFPE] slides or block) from archival tissue. Alternatively, a fresh biopsy should be collected, unless medically not justifiable to be conducted.

Have Eastern Cooperative Oncology Group performance status of 0 or 1.

Disqualifiers

Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 (including antibody, ADC, cell therapy, and other drugs) or with a topoisomerase I inhibitor payload (including topoisomerase I inhibitor-containing ADCs). Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.

Bleeding diathesis or active hemorrhage

Active infection, including respiratory viral infection

Child-Pugh class B or C cirrhosis

Trial design

Design model

Sequential

Treatments tested in this trial

  • BNT326

    Drug

    intravenous (IV) infusion

  • BNT327

    Drug

    IV infusion

  • Pembrolizumab

    Drug

    IV infusion

  • SoC

    Drug

    IV infusion. Combination chemotherapy (pemetrexed, paclitaxel, or carboplatin). Chemotherapy will be selected according to the indication.

Treatment groups

420 Participants
are divided into 15 treatment groups

15

Treatment groups

See each treatment group below.

Group A: Part 1 - BNT326 (DL1, starting dose) + BNT327Experimental treatment 2 interventions
Group B: Part 1 - BNT326 (DL2) + BNT327Experimental treatment 2 interventions
Group C: Part 1 - BNT326 (DL3, optional) + BNT327Experimental treatment 2 interventions
Group D: Part 2a (Cohort A, Arm 1) - BNT326 (DL1) + BNT327Experimental treatment 2 interventions
Group E: Part 2a (Cohort A, Arm 2) - BNT326 (DL2) + BNT327Experimental treatment 2 interventions
Group F: Part 2a (Cohort B, Arm 1) - BNT326 (DL1) + BNT327Experimental treatment 2 interventions
Group G: Part 2a (Cohort B, Arm 2) - BNT326 (DL2) + BNT327Experimental treatment 2 interventions
Group H: Part 2b (Cohort C, Arm 1) - BNT326 (DL1) + BNT327Experimental treatment 2 interventions
Group I: Part 2b (Cohort C, Arm 2) - BNT326 (DL2) + BNT327Experimental treatment 2 interventions
Group J: Part 2b (Cohort C, Arm 3) - BNT326 monotherapyExperimental treatment 1 intervention
Group K: Part 2b (Cohort D1, Arm 1) - BNT326 (DL2) + BNT327Experimental treatment 2 interventions
Group L: Part 2b (Cohort D1, Arm 2) - PembrolizumabActive comparator 1 intervention
Group M: Part 2b (Cohort D1, Arm 3) - BNT327 monotherapyExperimental treatment 1 intervention
Group N: Part 2b (Cohort D2, Arm 1) - BNT326 (DL2) + BNT327Experimental treatment 2 interventions
Group O: Part 2b (Cohort D2, Arm 2) - SoC - Pembrolizumab + chemotherapyActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant

During the DLT evaluation period by dose level

Time frame
21 days starting on Day 1 of Cycle 1
2

Part 1 and Part 2a - Occurrence of treatment emergent adverse events (TEAEs), treatment-related adverse events (TRAE), treatment emergent serious adverse events (TESAE), treatment-related serious adverse events (TRSAE)

Time frame
from the first dose of investigational medicinal product (IMP) up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
3

Part 1 and Part 2a - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs

Time frame
from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
4

Part 2a and Part 2b - Objective response rate (ORR)

Defined as the percentage of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.

Time frame
from the time of initiation of the first dose of IMP to approximately 36 months

Secondary outcomes

1

Part 1 - ORR

Defined as the percentage of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator's assessment) is observed as best overall response.

Time frame
from the time of initiation of the first dose of IMP to approximately 36 months
2

Part 2b - Occurrence of TEAEs, TRAEs, TESAEs, TRSAEs

Time frame
from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
3

Part 2b - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs

Time frame
from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
4

Part 2a and Part 2b - Progression free survival based on the investigator's assessment

Defined as the time from first dose of IMP to the first objective tumor progression (progressive disease \[PD\] per RECIST v1.1) or death from any cause, whichever occurs first.

Time frame
from the first dose of IMP to approximately 36 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

BioNTech SE

Lead sponsor

MediLink Therapeutics (Suzhou) Co., Ltd.

Collaborator