A Study to Learn about the Study Medicine called PF-08634404 in Combination With Chemotherapy in Adult Participants With Extensive Stage Small Cell Lung Cancer

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]

Decision date (initial)

2026-04-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2025-523522-41-00

ClinicalTrials.gov

NCT07226999

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Phase 2: To evaluate antitumor efficacy in PF-08634404 + chemotherapy, To evaluate safety and tolerability of PF-08634404 + chemotherapy ; Phase 3: To demonstrate that PF 08634404 + chemotherapy (experimental arm) is superior to atezolizumab + chemotherapy (control arm) in prolonging OS.

Secondary objectives 10

1. Phase 2: To evaluate additional measures of efficacy for PF-08634404 + chemotherapy
2. Phase 2: To evaluate additional measures of safety and tolerability for PF-08634404 + chemotherapy
3. Phase 2: To evaluate the PK of PF-08634404 when administered in combination with chemotherapy followed by single agent maintenance therapy
4. Phase 2: To evaluate the immunogenicity of PF-08634404 when administered in combination with chemotherapy followed by single agent maintenance therapy
5. Phase 3: To demonstrate that PF-08634404 + chemotherapy (experimental arm) is superior to atezolizumab + chemotherapy (control arm) in prolonging PFS by BICR.
6. Phase 3: To evaluate additional measures of efficacy for the experimental and control arms
7. Phase 3: To characterize the overall safety profile and tolerability of both treatment arms
8. Phase 3: To evaluate the PK of PF-08634404 when administered in combination with chemotherapy followed by single agent maintenance therapy
9. Phase 3: To evaluate the immunogenicity of PF-08634404 when administered in combination with chemotherapy followed by single agent maintenance therapy
10. Phase 3: To evaluate PROs for the experimental and control arms

Conditions and MedDRA coding

Extensive-Stage Small Cell Lung Cancer

Regulatory references

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 9

1. 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening. • Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. • Participants of childbearing potential (Section 10.4.3) must have a negative serum pregnancy test (minimum sensitivity 25 mIU/mL or equivalent quantitative assay) result within 72 hours prior to the first dose of study intervention. Participants with false positive results and documented verification that the participant is not pregnant are eligible for participation.
2. Have histologically or cytologically confirmed ES SCLC (using the American Joint Committee on Cancer [AJCC]) tumor node metastasis [TNM] staging system combined with Veterans Administration Lung Study Group two-stage classification scheme). For AJCC TNM staging system: AJCC 8th edition stage IV (T any, N any, M1a/b/c), or T3-4 for multiple lung nodules or tumor/nodule volume that cannot be encompassed in a tolerable radiotherapy plan. Note: Participants with a known history of non-small cell lung cancer (NSCLC) harboring actionable genomic alterations (AGAs), including but not limited to EGFR, ALK, ROS1, RET, MET, BRAF, NTRK, or HER2, who have undergone histologic transformation to small cell lung cancer (SCLC) are excluded.
3. Participants who have not received systemic therapy for ES-SCLC. Participants who received a single cycle of chemotherapy (without immune checkpoint inhibitors) for the management of life-threatening ES-SCLC (such as superior vena cava syndrome but no cord compression) may be eligible, once DLRT confirms 10 mg/kg dose is safe in the [CCI] patients and they meet all other eligibility criteria. Participants with prior systemic therapy for Limited-Stage Small-Cell Lung Cancer (LS-SCLC) must have been treated with curative intent and had a treatment-free interval of at least 6 months since the last systemic anticancer treatment including chemotherapy, radiotherapy, or chemoradiotherapy before the diagnosis of ES-SCLC to be eligible.
4. Have at least one measurable lesion as the targeted lesion based on RECIST V1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion).
5. Have sufficient tumor tissue available, either paraffin block or slides from a core, excisional or fine needle biopsy (FNA cytology samples which have not been prepared as an FFPE block, and biopsies containing bone are not adequate). a) Archival specimen from the most recent biopsy before the start of study intervention. See Central Laboratory Manual for tissue specifications, handling, and shipping instructions. b) If sufficient archival tissue is not available, a new baseline tumor biopsy with adequate tissue is required, unless medically infeasible and with prior agreement with the medical monitor.
6. Eastern Cooperative Oncology Group performance status of 0 or 1.
7. Have a minimum life expectancy of >12 weeks.
8. Have adequate organ function, as defined below: a) Participants must meet the hematologic criteria below without the use of transfusions or growth factors (platelet or red blood cell transfusions, TPO, EPO, G-CSF, IL-11, etc.) within 7 days prior to screening laboratory tests.
9. The participant must provide written informed consent.

Exclusion criteria 19

1. Participants with known active CNS lesions, including brainstem, meningeal, or spinal cord metastases or compression are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be enrolled if all of the following are met: • 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. • The participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention.
2. Leptomeningeal disease
3. Clinically significant risk of hemorrhage or fistula including but not limited to the following: a) Significant tumor necrosis or cavitation, b) The investigator deems that participation in the study poses a risk of hemorrhage; c) Tumor invasion or compression of surrounding critical organs (such as aorta, heart and pericardium, superior vena cava, trachea, and esophagus) or a risk of developing tracheoesophageal or pleuroesophageal fistula; d) Mediastinal lymph node metastasis with invasion of the trachea or main bronchi. If centrally located mediastinal masses (<30 mm from the carina) identified by CT scan or chest x-ray, CT scan with intravenous contrast or MRI within 21 days prior to randomization must exclude major airway or blood vessel invasion by tumor.
4. Participants with any history of another malignancy within 3 years before the first dose of study intervention, 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 OS ≥90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
5. Unresolved toxicities from prior anti-tumor therapy, that did not recover to NCI CTCAE v5.0 Grade 0 or 1, or to levels specified in the inclusion/exclusion criteria, with the exception of alopecia. Participants who experience irreversible toxicity that is not expected to worsen with continued administration of the study intervention (eg, hearing loss) may be enrolled in the study after consultation with the medical monitor. Participants with long-term toxicity from radiotherapy that is deemed irreversible by the investigator may be enrolled in the study after consultation with the medical monitor. Information should be provided to the medical monitor before proceeding.
6. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
7. Participants with active autoimmune diseases requiring systemic treatment within the past 2 years (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs) a) Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic disease modifying treatment and is allowed. b) Participants with vitiligo, psoriasis, type 1 diabetes mellitus (if not excluded per exclusion criterion 9i), or resolved childhood asthma/atopy are allowed. c) Participants requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections are allowed (if not excluded per exclusion criterion 8c). d) Participants with Sjögren’s syndrome are allowed (if not excluded per exclusion criterion 8c).
8. Participants with any of the following respiratory conditions: a) Evidence of non-infectious or drug induced ILD or pneumonitis that: • Was previously diagnosed and managed with parenteral steroids for any duration or oral steroids for >6 weeks, or • Had onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or • Is currently diagnosed and managed with systemic therapy, or • Is suspected on radiologic imaging at screening. • Participants who are asymptomatic and have radiographic findings of non-infectious, radiation-induced, or drug-induced ILD or pneumonitis confined to 1 bronchopulmonary segment or <10% of lung parenchyma may be enrolled after consultation with the medical monitor. b) Known 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. For thromboembolic events other than pulmonary emboli please refer to Exclusion Criterion 9k. • Any autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc).
9. History of uncontrolled comorbidities within 6 months prior to the first dose including: a) Unstable angina b) Myocardial infarction c) Uncontrolled or significant arrhythmia (including sustained ventricular tachyarrhythmia and ventricular fibrillation), untreated serious conduction system abnormalities (eg, bifascicular block [defined as right bundle branch and left anterior or posterior hemiblock], 3rd degree AV block) d) Coronary/peripheral artery bypass graft e) Transient ischemic attack, cerebrovascular accident, cerebral infarction (excluding lacunar infarction), or cerebral hemorrhage f) Symptomatic congestive heart failure or symptoms consistent with NYHA Functional Class III or IV g) Decompensated liver cirrhosis h) Nephrotic syndrome i) Uncontrolled diabetes defined as HbA1c ≥8.0% or HbA1c between 7.0% and 8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained (or poor compliance with hypoglycemic medications) j) Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, or poor compliance with antihypertensive medications) k) Arterial thromboembolic event and venous thromboembolic event Grade >3 as specified in CTCAE 5.0 l) Hypertensive crisis m) Hypertensive encephalopathy n) Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN)
10. Baseline QTcF interval > 480 msec • If QTcF exceeds 480 msec, the ECG should be repeated twice and the average of the 3 QTcF values should be used to determine the participant’s eligibility. Computer-interpreted ECGs with abnormal findings should be overread by an investigator physician experienced in reading ECGs before excluding participants
11. Major surgery or severe trauma within 4 weeks prior to the first dose, or planned major surgery during the study; minor local surgery (excluding peripherally inserted central catheter placement and implantable central venous port placement) within 3 days prior to the first dose. Participants must have recovered adequately from the toxicity or complications from the surgery prior to starting study intervention.
12. Participants with pleural effusion, pericardial effusion, or ascites that are clinically symptomatic or require repeated drainage (once a month or more frequently).
13. History of severe bleeding tendency or coagulation dysfunction, such as presence of clinically significant bleeding symptoms within 1 month prior to the first dose, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing up or expectorating ≥½ teaspoon of fresh blood or small blood clots or coughing up blood without sputum; participants with blood-streaked sputum are allowed to be enrolled), or epistaxis (excluding minor nosebleeds and blood-tinged nasal discharge).
14. History of esophageal varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose;
15. Participants with acute, chronic or symptomatic infections including: a) Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted. b) Known seropositivity of HIV, except for participants with controlled HIV infection on a stable regimen of ART (CD4+ count >200/mm3 and viral load of <400 copies/mL). The investigator will ensure the ART does not result in substantial interactions with study or concomitant medications. c) Positive for HBV by surface antigen expression. d) Active HCV infection (positive by PCR). Participants who have been treated for HCV infection are eligible if they have documented sustained virologic response 12 weeks after completion of antiviral therapy. e) Testing for HIV, HBV, or HCV is not required unless mandated by local health authorities. f) Participants with known active TB infection • participants suspected to have active TB are required to undergo clinical evaluation to rule out the condition;
16. Participants with history of immunodeficiency
17. Known history of a severe allergic reaction including anaphylaxis or CTCAE Grade ≥3 hypersensitivity reactions, to any active substance or excipients of the study interventions (including PF-08634404, atezolizumab, carboplatin and etoposide), or a history of severe allergic reaction to chimeric or humanized antibody
18. Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
19. Other circumstances that may increase the study-related risks or interfere with interpretation of the study results, in the opinion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 2: • Confirmed ORR as assessed by investigator based on RECIST v1.1 • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
2. Phase 3: • OS

Secondary endpoints 13

1. Phase 2 • DOR as assessed by investigator based on RECIST v1.1 • PFS as assessed by investigator based on RECIST v1.1 • OS
2. Phase 2 • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. • DLTs
3. Phase 2 • Predose and postdose concentrations of PF 08634404.
4. Phase 2 • Incidence of ADA against PF-08634404.
5. Phase 3 • PFS using RECIST v1.1 as assessed by BICR
6. Phase 3 • Confirmed ORR using RECIST v1.1 as assessed by BICR • Confirmed ORR using RECIST v1.1 as assessed by investigator
7. Phase 3 • PFS using RECIST v1.1 as assessed by investigator
8. Phase 3 • DOR using RECIST v1.1 as assessed by BICR • DOR using RECIST v1.1 as assessed by investigator
9. Phase 3 • AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s).
10. Phase 3 • Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing.
11. Phase 3 • Predose and postdose concentrations of PF 08634404.
12. Phase 3 • Incidence of ADA against PF 08634404.
13. Phase 3 • Mean scores and change from baseline in the global health status/QoL, function, and symptom scores on the EORTC QLQ-C30 • Mean scores and change from baseline on the EORTC QLQ-LC13 • Time to definitive deterioration in the global health status/QoL, function, and symptom scores on the EORTC QLQ-C30 • Time to definitive deterioration in dyspnea, cough, or chest pain on the EORTC QLQ-LC13

Investigational products

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

Test 3

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 15

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Results and documents

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

Documents 35 files

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

Application history

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