A Study to Learn About the Study Medicine Called PF-08046054/SGNPDL1V Versus Docetaxel in Adult Participants with Previously-treated Programmed Cell Death Ligand 1 (PD-L1) Positive Non-small-cell Lung Cancer (NSCLC)

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

2 Dec 2025 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacokinetic, Pharmacodynamic, Safety

To compare the overall survival (OS) between the experimental arm (PF-08046054) and control arm (docetaxel) in participants with tumor PD-L1 ≥1% (all participants) and participants with tumor PD-L1 ≥50%

Secondary objectives 11

1. To compare the objective response rate (ORR) as assessed by BICR between the experimental and control arms in participants with tumor PD-L1 ≥1% (all participants) and participants with tumor PD-L1 ≥50%
2. To assess PFS as assessed by investigator between the experimental and control arms
3. To assess the ORR as assessed by investigator between the experimental and control arms
4. To estimate the duration of response (DOR) as assessed by BICR for the experimental and control arms
5. To estimate DOR as assessed by investigator for the experimental and control arms
6. To characterize the safety and tolerability profile of PF-08046054
7. To assess change in quality of life (QoL), functioning, and lung cancer symptom response between the experimental and control arms
8. To assess time to definitive deterioration (TTdD) in QoL, functioning, and lung cancer symptoms between the experimental and control arms
9. To characterize the pharmacokinetics (PK) of PF-08046054
10. To characterize the immunogenicity of PF- 08046054
11. To compare progression-free survival (PFS) as assessed by blinded independent central review (BICR) between the experimental and control arms in participants with tumor PD-L1 ≥1% (all participants) and participants with tumor PD-L1 ≥50%

Conditions and MedDRA coding

Non-Small Cell Lung Cancer (NSCLC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

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 5

1. Histologically or cytologically confirmed diagnosis of NSCLC with locally advanced, unresectable Stage IIIB or IIIC not eligible for definitive chemoradiotherapy or metastatic (Stage IV: M1a, M1b, or M1c) disease per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System. Note: Participants with a neuroendocrine component or histology are not eligible.
2. PD-L1 expression on ≥1% of tumor cells based on local immunohistochemistry (IHC) testing with an assay utilizing the anti-PD-L1 monoclonal antibody clones 22C3 or SP263
3. Participants who have NSCLC with known AGAs are permitted.
4. Able to provide any of the following tumor tissues for biomarker analysis: • Archival specimen (preferably collected within 12 months after the last anticancer therapy) (see laboratory manual for details); or • De novo biopsy from a tumor lesion, if medically feasible.
5. Participants must have received the following therapies and progressed during or relapsed after receiving their most recent prior therapy, or have been intolerant to their most recent therapy: - Participants with no known AGAs must fulfill 1 of the following conditions: o Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, and unless contraindicated, a PD(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy). o Experience disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting and received a PD(L)1 monoclonal antibody at any time during the course of treatment.  Participants with known AGAs (eg, EGFR mutations, ALK translocations, or other relevant actionable mutations) must fulfill the following conditions: o Must have received at least 1 relevant AGA-targeted therapy if locally available and, in the opinion of the investigator, additional AGA-targeted therapy is not in the best interest of the participant o Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting. o May have received PD-[L]1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).

Exclusion criteria 5

1. History of another malignancy within 3 years before the first dose of PF- 08046054, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] ≥90%), such as adequately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
2. Any central nervous system (CNS) lesions, unless definitively treated with CNS-directed local therapy (surgery and/or radiotherapy) Participants with definitively treated brain metastases are eligible if they meet the following criteria:  The participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least >14 days prior to randomization (if requiring steroid treatment).  No clinical or radiographic progression in the CNS following CNS-directed definitive radiotherapy and/or surgery.  Time since CNS-directed treatment is ≥28 days prior to randomization.
3. Participants with a history of leptomeningeal metastasis are excluded.
4. Prior treatment with an anti-PD-L1 agent (where indicated per protocol) within 5 half-lives.
5. Previous receipt of an MMAE-containing agent or prior docetaxel.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS)

Secondary endpoints 15

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. 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. Mean scores and change from baseline in the global health status/QoL score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
8. Mean scores and change from baseline in physical functioning and role functioning scores on the EORTC QLQ-C30
9. Mean scores and change from baseline in dyspnea, cough, and chest pain scores on the EORTC Quality of Life Cancer Questionnaire – Lung Cancer 13 QLQ-LC13
10. TTdD in the global health status/QoL score on the EORTC QLQ-C30
11. TTdD in physical functioning and role functioning scores on the EORTC QLQ-C30
12. TTdD in the dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13
13. Plasma concentration at end of infusion and plasma predose concentration for antibody conjugated monomethyl auristatin E (ac-MMAE) and unconjugated monomethyl auristatin E (MMAE) (in PF-08046054 treatment arm only)
14. Incidence of ADAs (in PF-08046054 treatment arm only)
15. PFS using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) as assessed by BICR

Investigational products

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

Test 1

Comparator 1

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 20

Locations

14 EU/EEA countries · 103 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 186 files

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

Application history

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