A Study to Learn About the Study Medicine Called Sigvotatug Vedotin in People with Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer with High Levels of PD-L1 (Be6A Lung-02)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Jul 2025 → ongoing

Decision date (initial)

2025-09-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-517968-36-00

ClinicalTrials.gov

NCT06758401

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Efficacy, Pharmacokinetic, Others, Safety

To demonstrate that sigvotatug vedotin with pembrolizumab (experimental arm) is superior to pembrolizumab alone (control arm) in prolonging OS.
To demonstrate that sigvotatug vedotin with pembrolizumab (experimental arm) is superior to pembrolizumab alone (control arm) in prolonging PFS by blinded independent central review (BICR).

Secondary objectives 5

1. To compare objective response rate (ORR) by BICR between the experimental and control arms
2. To evaluate additional measures of efficacy for the experimental and control arms
3. To characterize the safety and tolerability profile of both treatment arms
4. To characterize the pharmacokinetics (PK) of sigvotatug vedotin when administered in combination with pembrolizumab
5. To characterize the immunogenicity of sigvotatug vedotin when administered in combination with pembrolizumab

Conditions and MedDRA coding

non-small cell lung cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Participants must meet the following criteria: a. 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening. b. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. c. Participants must have adequate baseline hematologic, hepatic, and renal function. d. Have pathologically confirmed Stage IIIB or IIIC NSCLC and not be a candidate for surgical resection or definitive chemoradiation, or Stage IV NSCLC per the American Joint Committee on Cancer (AJCC) Staging Manual (Version 8.0) and the Union for International Cancer Control (UICC) Staging System (Eighth edition). e. Participants with non-squamous histology must have documented negative test results for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) actionable genomic alterations (AGAs) and no known AGAs in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET),mesenchymal-epithelial transition factor (MET), or other AGAs with approved front-line therapies per local standard of care. f. Must not have small cell elements present. g. Large cell neuroendocrine carcinoma is excluded. h. Must be an appropriate candidate for treatment with pembrolizumab monotherapy per local guidelines.
2. Tumor has PD-L1 expression in ≥50% of tumor cells as determined by local testing with retrospective central confirmation using a PD-L1 IHC assay. a. Tumor sample (formalin fixed paraffin embedded [FFPE]) acquired at screening must be collected according to Laboratory Manual standards and must be made available to the Sponsor for central laboratory confirmation. b. Archival tumor specimen that has been collected within 6 months prior to first dose of study intervention may be used. c. If no archival tissue is available, the participant must be willing and able to undergo a biopsy procedure to obtain a tumor tissue specimen.
3. Measurable disease based on RECIST v1.1 per investigator. Participants with prior definitive radiotherapy must have measurable disease per RECIST v1.1 that is outside the radiation field or have unequivocal progression of previously irradiated lesions (see exclusion criterion 15c in full protocol).

Exclusion criteria 3

1. Prior and concomitant therapy: a. Any prior treatment with MMAE derived drugs or integrin beta-6 targeting agents. b. Prior systemic therapy, including anti-PD-L1 or anti-programmed cell death receptor 1 (PD-1, collectively PD-[L]1) therapy, for locally advanced, unresectable, or metastatic NSCLC.  (Neo)adjuvant anti-PD-(L)1 is allowed if recurrence or progression occurred ≥9 months after the last dose.  Other (neo)adjuvant or definitive therapy is allowed if recurrence or progression occurred ≥6 months after the last dose. c. Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received. d. Chemotherapy, biologics, and/or other antitumor treatment with immunotherapy not specifically prohibited that is completed less than 4 weeks prior to first dose of study intervention, or 2 weeks for palliative radiotherapy.  Participants must have recovered from all radiation related toxicities that would otherwise prevent trial participation.  Ongoing hormonal/antihormonal treatment (eg, for breast cancer, prostate cancer) is allowed, provided that the participant is eligible per synopsis exclusion criterion 3. e. Current therapy with an investigational agent. f. Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor (eg, CTLA4, LAG-3, TIGIT, OX 40, 41-BB, PD-L2, CD137). g. Treatment with any prohibited concomitant therapy within 21 days of the first dose of study intervention.
2. Participants with any of the following respiratory conditions: a. Evidence of noninfectious or drug-induced ILD or pneumonitis that:  Was previously diagnosed and required systemic steroids, or  Is currently diagnosed and managed, or  Is suspected on radiologic imaging at screening b. Known diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) <50% predicted. c. Any Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to:  Severe asthma requiring systemic corticosteroids within 30 days prior to first dose of study intervention or not well controlled with low-dose inhaled corticosteroids/long-acting beta-2 agonists.  Severe chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids.  Clinically severe and/or Grade 4 pulmonary emboli within 3 months of the first dose of study intervention. Pulmonary emboli in main or lobar pulmonary arteries are also excluded.  Any autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjogren’s syndrome, sarcoidosis, etc).
3. Known active central nervous system (CNS) lesions, including leptomeningeal metastasis, are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) are eligible if they meet the following criteria: a. CNS metastases have been clinically stable with no evidence of clinical or radiographic disease progression for ≥14 days after completion of definitive radiotherapy and/or surgery and prior to study intervention. b. The participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention. c. Clinically inactive brain metastases of longest diameter <0.5 cm are permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. OS
2. PFS using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) as assessed by BICR

Secondary endpoints 8

1. Confirmed ORR using RECIST v1.1 as assessed by BICR
2. PFS using RECIST v1.1 as assessed by investigator
3. Confirmed ORR using RECIST v1.1 as assessed by investigator
4. Duration of response (DOR) using RECIST v1.1 as assessed by BICR
5. DOR using RECIST v1.1 as assessed by investigator
6. Type, incidence, severity, seriousness, and relatedness of adverse events (AEs)
7. Plasma concentration at end of infusion (CEOI) and Plasma predose concentration (Cpredose) for antibody conjugated monomethyl auristatin E (ac-MMAE) and unconjugated monomethyl auristatin E (MMAE)
8. Incidence of antidrug antibodies (ADAs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 12

Locations

15 EU/EEA countries · 126 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 175 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

18 submissions — initial application plus substantial / non-substantial modifications