A Phase 3 interventional study of PF-08634404 and Pembrolizumab in Advanced Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer and Carcinoma, Non-Small-Cell Lung, sponsored by Pfizer. Recruiting at 479 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Pfizer · Phase 3, Interventional, and Treatment
This study is being done to find out if a new medicine called PF-08634404, when given with chemotherapy, works better than the present standard treatment (pembrolizumab with chemotherapy) for adults with a type of lung cancer called non-small cell lung cancer (NSCLC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body.
To join the study, participants must meet the following conditions:
Participants in this study will be assigned to two different parts of the study depending on their type of tumor: participants with squamous NSCLC will be assigned to Part 1, while participants with non-squamous NSCLC will be assigned to Part 2.
Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups in a blinded fashion:
Participants will receive their assigned treatment through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, participants will receive PF-08634404 or Pembrolizumab in combination with chemotherapy followed by maintenance with either PF-08634404 or Pembrolizumab monotherapy (Part 1) or PF-08634404 or Pembrolizumab in combination with a chemotherapeutic drug (Part 2). Participants will continue receiving treatment if it is helping and not experiencing serious side effects.
The study will include regular visits for:
Exclusion Criteria:
Previous systemic anti-tumor therapy including:
Prior and concomitant therapy:
Participants will receive PF-08634404 combined with chemotherapy regimen 1, followed by maintenance therapy with PF-08634404.
Biological: PF-08634404 · Drug: Chemotherapy Regimen 1
Participants will receive pembrolizumab combined with chemotherapy regimen 1, followed by maintenance therapy with pembrolizumab.
Biological: Pembrolizumab · Drug: Chemotherapy Regimen 1
Participants will receive PF-08634404 combined with chemotherapy regimen 2, followed by maintenance therapy with PF-08634404 and chemotherapy.
Biological: PF-08634404 · Drug: Chemotherapy Regimen 2
Participants will receive pembrolizumab combined with chemotherapy regimen 2, followed by maintenance therapy with pembrolizumab and chemotherapy.
Biological: Pembrolizumab · Drug: Chemotherapy Regimen 2
Solution for infusion
Injection for IV use
Injection for IV use
Injection for IV use
Overall Survival
Overall survival defined as the time from the date of randomization to the date of death due to any cause.
Time frame: Approximately 39 months
Progression Free Survival (PFS) assessed by blinded independent central review (BICR)
Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective progressive disease (PD) assessed by BICR per RECIST v1.1, or death due to any cause, whichever occurs first.
Time frame: Approximately 32 months
Confirmed objective response rate (ORR) using RECIST v1.1 as assessed by BICR
ORR is defined as the proportion of participants in the analysis population having a best overall response (BOR) of confirmed CR or confirmed PR according to RECIST v1.1 as assessed by BICR.
Time frame: Approximately 32 months
Progression Free Survival as assessed by Investigator
Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by investigator per RECIST v1.1, or death due to any cause, whichever occurs first.
Time frame: Approximately 32 months
Confirmed ORR using RECIST v1.1 as assessed by investigator
ORR is defined as the proportion of participants in the analysis population having a BOR of confirmed CR or confirmed PR according to RECIST v1.1 as assessed by BICR.
Time frame: Approximately 32 months
Duration of Response (DoR) as assessed by BICR
The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first.
Time frame: Approximately 32 months
Duration of Response (DoR) as assessed by Investigator
The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first.
Time frame: Approximately 32 months
Number of Participants With Adverse Events (AEs)
AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s).
Time frame: Through end of study and up to approximately 39 months
Number of Participants With Clinical Laboratory Abnormalities
Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing.
Time frame: through end of study and up to approximately 39 months
Pharmacokinetics (PK): Serum concentrations of PF-08634404
Predose and postdose concentrations of PF-08634404
Time frame: Through end of study and up to approximately 39 months
Incidence of Anti-Drug Antibody (ADA) against PF-08634404.
Time frame: Through end of study and up to approximately 39 months
Mean scores and Change from baseline in the global health status/quality of life (QoL) and physical function scores on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 is a questionnaire for quantitative measure of health-related quality of life pertinent to participants with a broad range of cancers who are participating in international clinical trials.
Time frame: Approximately 39 months
Time to definitive deterioration (TTdD) in in the global health status/QoL and physical function scores on the EORTC QLQ-C30
TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery.
Time frame: Approximately 39 months
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
EORTC QLQ-LC13 is a lung cancer specific module that serves as an additional 13 item questionnaire to the general EORTC cancer questionnaire, the EORTC QLQ-C30.
Time frame: Approximately 39 months
TTdD in the dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13
TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery.
Time frame: Approximately 39 months
Showing the first 100 of 479 sites across 20 countries.
Plan to share: Yes — 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.
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