PF-08634404 for Extensive-stage small cell lung cancer

Inclusion criteria

• {"criterion_text":"-18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening. •\tRefer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. •\tParticipants 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.\n- 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.\n- 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.\n- 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).\n- 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.\n- Eastern Cooperative Oncology Group performance status of 0 or 1.\n- Have a minimum life expectancy of >12 weeks.\n- Have adequate organ function, as defined below: a)\tParticipants 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.\n- The participant must provide written informed consent."}

Exclusion criteria

• {"criterion_text":"-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: •\tCNS 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. •\tThe participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention.\n-Baseline QTcF interval > 480 msec •\tIf 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\n-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.\n-Participants with pleural effusion, pericardial effusion, or ascites that are clinically symptomatic or require repeated drainage (once a month or more frequently).\n-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).\n-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;\n-Participants with acute, chronic or symptomatic infections including: a)\tCurrently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted. b)\tKnown 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)\tPositive for HBV by surface antigen expression. d)\tActive 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)\tTesting for HIV, HBV, or HCV is not required unless mandated by local health authorities. f)\tParticipants with known active TB infection •\tparticipants suspected to have active TB are required to undergo clinical evaluation to rule out the condition;\n-Participants with history of immunodeficiency\n-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\n-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.\n-Other circumstances that may increase the study-related risks or interfere with interpretation of the study results, in the opinion of the investigator.\n-Leptomeningeal disease\n-Clinically significant risk of hemorrhage or fistula including but not limited to the following: a)\tSignificant tumor necrosis or cavitation, b)\tThe investigator deems that participation in the study poses a risk of hemorrhage; c)\tTumor 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)\tMediastinal 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.\n-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.\n-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.\n-History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.\n-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)\tReplacement 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)\tParticipants with vitiligo, psoriasis, type 1 diabetes mellitus (if not excluded per exclusion criterion 9i), or resolved childhood asthma/atopy are allowed. c)\tParticipants requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections are allowed (if not excluded per exclusion criterion 8c). d)\tParticipants with Sjögren’s syndrome are allowed (if not excluded per exclusion criterion 8c).\n-Participants with any of the following respiratory conditions: a)\tEvidence of non-infectious or drug induced ILD or pneumonitis that: •\tWas previously diagnosed and managed with parenteral steroids for any duration or oral steroids for >6 weeks, or •\tHad onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or •\tIs currently diagnosed and managed with systemic therapy, or •\tIs suspected on radiologic imaging at screening. •\tParticipants 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)\tKnown DLCO (adjusted for hemoglobin) <50% predicted. c)\tAny Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to: •\tSevere 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. •\tSevere chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids. •\tClinically 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. •\tAny autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc)."}

Primary endpoints

• {"endpoint_text":"-Phase 2: •\tConfirmed ORR as assessed by investigator based on RECIST v1.1 •\tAEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.","definition_or_measurement_approach":"Confirmed ORR as assessed by investigator based on RECIST v1.1; AEs characterised by type, frequency, severity graded by NCI CTCAE v5.0, timing, seriousness and relationship to study intervention."}
• {"endpoint_text":"-Phase 3: •\tOS","definition_or_measurement_approach":"Overall survival (OS)."}

Secondary endpoints

• {"endpoint_text":"-Phase 2 •\tDOR as assessed by investigator based on RECIST v1.1 •\tPFS as assessed by investigator based on RECIST v1.1 •\tOS","definition_or_measurement_approach":"DOR and PFS assessed by investigator per RECIST v1.1; OS as overall survival."}
• {"endpoint_text":"-Phase 2 •\tLaboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. •\tDLTs","definition_or_measurement_approach":"Laboratory abnormalities graded by NCI CTCAE v5.0; DLTs as defined in protocol (dose-limiting toxicities)."}
• {"endpoint_text":"-Phase 2 •\tPredose and postdose concentrations of PF 08634404.","definition_or_measurement_approach":"Pharmacokinetic sampling for PF-08634404 predose and postdose concentrations."}
• {"endpoint_text":"-Phase 2 •\tIncidence of ADA against PF-08634404.","definition_or_measurement_approach":"Incidence of anti-drug antibodies (ADA) against PF-08634404."}
• {"endpoint_text":"-Phase 3 •\tPFS using RECIST v1.1 as assessed by BICR","definition_or_measurement_approach":"Progression-free survival per RECIST v1.1 assessed by blinded independent central review (BICR)."}
• {"endpoint_text":"-Phase 3 •\tConfirmed ORR using RECIST v1.1 as assessed by BICR •\tConfirmed ORR using RECIST v1.1 as assessed by investigator","definition_or_measurement_approach":"Confirmed ORR per RECIST v1.1 assessed by both BICR and investigator."}
• {"endpoint_text":"-Phase 3 •\tPFS using RECIST v1.1 as assessed by investigator","definition_or_measurement_approach":"Investigator-assessed PFS per RECIST v1.1."}
• {"endpoint_text":"-Phase 3 •\tDOR using RECIST v1.1 as assessed by BICR •\tDOR using RECIST v1.1 as assessed by investigator","definition_or_measurement_approach":"Duration of response (DOR) per RECIST v1.1 assessed by BICR and investigator."}
• {"endpoint_text":"-Phase 3 •\tAEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s).","definition_or_measurement_approach":"Adverse events characterised by type, frequency, severity graded by NCI CTCAE v5.0, timing, seriousness and relationship to study interventions."}
• {"endpoint_text":"-Phase 3 •\tLaboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing.","definition_or_measurement_approach":"Laboratory abnormalities graded per NCI CTCAE v5.0."}
• {"endpoint_text":"-Phase 3 •\tPredose and postdose concentrations of PF 08634404.","definition_or_measurement_approach":"Pharmacokinetic assessments predose and postdose for PF-08634404."}
• {"endpoint_text":"-Phase 3 •\tIncidence of ADA against PF 08634404.","definition_or_measurement_approach":"Incidence of anti-drug antibodies against PF-08634404."}
• {"endpoint_text":"-Phase 3 •\tMean scores and change from baseline in the global health status/QoL, function, and symptom scores on the EORTC QLQ-C30 •\tMean scores and change from baseline on the EORTC QLQ-LC13 •\tTime to definitive deterioration in the global health status/QoL, function, and symptom scores on the EORTC QLQ-C30 •\tTime to definitive deterioration in dyspnea, cough, or chest pain on the EORTC QLQ-LC13","definition_or_measurement_approach":"Patient-reported outcomes measured by EORTC QLQ-C30 and QLQ-LC13; change from baseline and time to definitive deterioration."}

Methods

• Continuum Clinical LLC (United States) – duty: Recruitment and Retention (listed as sponsor third party responsible for recruitment and retention).
• Innovative Trials Limited (United Kingdom) – duty: Recruitment and Retention (listed as sponsor third party responsible for recruitment and retention).
• WCG Clinical Inc. (United States) – duty: Recruitment and Retention (listed as sponsor third party responsible for recruitment and retention).
• Omnitrace Corp. (United States) – duty: Recruitment and Retention (listed as sponsor third party responsible for recruitment and retention).
• Scout Clinical (United States) – duty: Study participant payments (listed as sponsor third party involved in participant payments).
• Sponsor recruitment arrangements documents (K1) exist for France, Germany, Italy and Spain (titles present in public documents), but specific channel/advertising/registry details are not provided in the available records.

France

Earliest CTIS Part Ii Submission Date

27-02-2026

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

39

Number Of Sites

2

Number Of Participants

47

Germany

Earliest CTIS Part Ii Submission Date

18-03-2026

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

23

Number Of Sites

2

Number Of Participants

29

Italy

Earliest CTIS Part Ii Submission Date

27-02-2026

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

41

Number Of Sites

3

Number Of Participants

52

Spain

Earliest CTIS Part Ii Submission Date

06-03-2026

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

34

Number Of Sites

5

Number Of Participants

54

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

QPS LLC

Responsibilities

code:4

Name

IQVIA Limited

Responsibilities

code:7

Name

Continuum Clinical LLC

Responsibilities

Recruitment and Retention

Name

Bioclinica Inc.

Responsibilities

Medical Imaging services

Name

Innovative Trials Limited

Responsibilities

Recruitment and Retention

Name

WCG Clinical Inc.

Responsibilities

Recruitment and Retention

Name

Guardant Health Inc.

Responsibilities

code:4

Name

Scout Clinical

Responsibilities

Study participant payments

Name

Icon Development Solutions LLC

Responsibilities

code:4

Name

Omnitrace Corp.

Responsibilities

Recruitment and Retention

Name

CellCarta

Responsibilities

code:4

Name

PAREXEL International GmbH

Responsibilities

Clinical supplies and equipment provision; Drug destruction

Name

Personalis Inc.

Responsibilities

code:4

Name

PPD Development LP

Responsibilities

code:4

Name

Fulgent Genetics Inc.

Responsibilities

code:4

Third parties

• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code:7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Continuum Clinical LLC","duties_or_roles":"Recruitment and Retention","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical Imaging services","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Innovative Trials Limited","duties_or_roles":"Recruitment and Retention","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Recruitment and Retention","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Study participant payments","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Omnitrace Corp.","duties_or_roles":"Recruitment and Retention","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"PAREXEL International GmbH","duties_or_roles":"Clinical supplies and equipment provision; Drug destruction","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Personalis Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Fulgent Genetics Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}