Safety and Preliminary Efficacy of Pumitamig (BNT327), an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy as First-line or Second-line Treatment

ConditionNon-small Cell Lung Cancer

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorBioNTech SE

About this trial

This is a Phase II, multisite, open-label study consisting of two parts in participants with advanced/metastatic Non-small Cell Lung Cancer (NSCLC) which progressed after a first-line chemoimmunotherapy to evaluate the combination of pumitamig (also known as BNT327, BMS-986545 or PM8002) with standard of care.

Part 1 is a safety run-in with pumitamig (Dose 1 or Dose 2) plus docetaxel and will include up to 12 participants in total to be treated in Part 1A and 1B sequentially.

Part 2 is a dose expansion at the deemed safe dose of pumitamig plus docetaxel and will include up to 54 participants.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Have histologically or cytologically confirmed diagnosis of Stage IV NSCLC that has documented radiographic progression on one or after one prior line of systemic treatment (programmed death-1 [PD-1]/ programmed death ligand-1 [PD-L1] inhibitor and platinum-based chemotherapy concomitantly) in advanced/metastatic setting per the American Joint Committee on Cancer staging system, 9th edition.

Participants must have received minimum two cycles of immunotherapy in first-line treatment to be eligible to this study.

Only one prior line of immunotherapy containing regimen is allowed in an advanced/metastatic setting. If participant had received adjuvant immunotherapy the disease-free interval (after the last dose of adjuvant immunotherapy) should be at least 6 months.

Historical PD-L1 results must be available.

Disqualifiers

Have a known or suspected hypersensitivity to the study treatments, their metabolites or formulation of excipients including polysorbate 80 (see Docetaxel label).

Participants who received prior treatment with anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or anti-PD-(L)-1/aVEGF bispecific antibody or docetaxel as monotherapy or in combination with other agents.

Have received more than one prior lines of therapies in advanced/metastatic setting.

Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of study treatment (except for docetaxel premedication). 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.

Trial design

Design model

Sequential

Treatments tested in this trial

Pumitamig
Drug
Intravenous infusion
Docetaxel
Drug
Intravenous infusion

Treatment groups

60 Participants

are divided into 3 treatment groups

Group A: Part 1A - Pumitamig Dose 1 + docetaxelExperimental treatment 2 interventions

Group B: Part 1B - Pumitamig Dose 2 + docetaxelExperimental treatment 2 interventions

Group C: Part 2: Selected doses of pumitamig + docetaxelExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Part 1 - Occurrence of dose limiting toxicities (DLTs)

During the DLT evaluation period by dose level

Time frame

Up to 21 days after first dose of investigational medicinal product (IMP)

Part 1 and Part 2 - Occurrence of pumitamig treatment emergent adverse events, treatment-related adverse events, treatment emergent serious adverse events, treatment-related serious adverse events, and adverse events of special interest

Graded according to the (United States) National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)

Time frame

From initiation of the first dose of IMP to the 90-day Follow-Up visit

Part 1 and Part 2 - Occurrence of dose interruption, dose reduction, and/or participant discontinuation due to adverse events

Time frame

From initiation of the first dose of IMP until the 90-day Safety Follow-up visit

Part 1 and Part 2 - Objective response rate

Defined as the proportion 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 investigator's review) is observed as best overall response.

Time frame

Up to approximately 2 years

Secondary outcomes

Part 1 and Part 2 - Duration of Response

Defined as the time from first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment) to first occurrence of objective tumor progression (progressive disease, per RECIST v1.1 based on the investigator's assessment) or death from any cause, whichever occurs first.

Time frame

Up to approximately 2 years

Part 1 and Part 2- 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 per RECIST v1.1) or death from any cause, whichever occurs first.

Time frame

Up to approximately 2 years

Part 1 and Part 2 - Depth of Response

Defined as the maximum percent reduction from baseline in tumor size measured by sum of target lesion diameter (including nodal \[short axis\] and non-nodal \[longest axis\] lesions).

Time frame

Up to approximately 2 years

Part 1 and Part 2 - Disease Control Rate

Defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease (per RECIST v1.1 based on the investigator's assessment) as best overall response.

Time frame

Up to approximately 2 years