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NCT07476287PHASE2Recruiting

Symbiotic-Lung-14: A Study to Learn About the Study Medicine Called PF08634404 in Combination With Chemotherapy in Adult Participants With Transformed Small Cell Lung Cancer

Pfizer

Start Date

7/2/2026

Completion Date

3/24/2031

Summary

This study is being done to learn more about a new medicine called PF-08634404. The study team wants to understand how well PF-08634404 works when given alone or with chemotherapy . Chemotherapy is a type of cancer treatment that uses medicines to destroy cancer cells or stop them from growing. The study is for adults with Transformed Small Cell Lung Cancer (T-SCLC ). T SCLC is a rare lung cancer that happens when one type of lung cancer changes into a more aggressive type after treatment stops working. To join the study, participants must meet the following conditions: * Are aged 18 years or older * Diagnosed with T-SCLC and have not received treatment for this type of lung cancer (a single cycle of chemotherapy may be permitted) * Prior diagnosis of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer treated with tyrosine kinase inhibitors (TKIs) * Have healthy organs based on medical tests and are in good physical condition After joining the study, adults will be given chemotherapy in addition to the study medicine. After this combination treatment is finished, the study medicine will be continued alone. Adults will receive the treatment through IV infusions (medicine given directly into a vein). All treatments will be done at clinical study sites, where a trained medical team will monitor adults during and after each visit.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Male or female participants aged ≥18 years at the time of informed consent. * Histologically or cytologically confirmed T-SCLC. Participant must have had a prior diagnosis of NSCLC with EGFR mutation which transformed to SCLC following the treatment with TKI(s). * Participants have not received systemic therapy for T-SCLC. * Have at least one measurable lesion as the target lesion based on RECIST v1.1. * Have sufficient tumor tissue from the diagnosis of transformed SCLC available. * Eastern Cooperative Oncology Group performance status of 0 or 1. * Have a minimum life expectancy of \>12 weeks. * Clinical laboratory values at screening within acceptable limits, as defined in the protocol, including: 1) Hematology, 2) Liver function and 3) Renal function. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: * Active or untreated CNS disease, including brain, brainstem, spinal cord, or meningeal metastases. Participants with definitively treated, clinically stable brain metastases may be eligible per protocol criteria. Participants with untreated asymptomatic brain metastases of longest diameter \<1 cm are permitted if all of the following criteria are met: absence of neurological symptoms, no need for corticosteroids, and brain metastasis has no evidence of edema or hemorrhagic features. * Leptomeningeal disease * Clinically significant risk of hemorrhage or fistula, including tumor necrosis/cavitation, invasion or compression of major blood vessels, airways, or critical organs, or risk of tracheoesophageal or pleuroesophageal fistula * History of another malignancy (other than NSCLC) within 3 years prior to first dose, except for malignancies with negligible risk of metastasis or death (eg, adequately treated carcinoma in situ, nonmelanoma skin cancer) * Unresolved toxicity from prior anti-tumor therapy that has not recovered to Grade ≤1 per NCI CTCAE v5.0 (except alopecia or irreversible toxicities deemed stable) * History of allogeneic organ or hematopoietic stem cell transplantation * Active autoimmune disease requiring systemic treatment within the past 2 years (Stable replacement therapy and selected low-risk autoimmune conditions are permitted per protocol) * Interstitial lung disease (ILD), pneumonitis, or significant pulmonary disease, including: * Prior or current non-infectious pneumonitis requiring systemic therapy * DLCO \<50% predicted * Severe asthma, COPD, pulmonary embolism, or autoimmune lung involvement * Uncontrolled or clinically significant cardiovascular, cerebrovascular, metabolic, hepatic, or renal disease within 6 months prior to first dose * Baseline QTcF \>480 msec * Major surgery or severe trauma within 4 weeks prior to first dose, or planned major surgery during the study * Clinically significant pleural effusion, pericardial effusion, or ascites requiring repeated drainage * History of significant bleeding disorders or recent major bleeding events * Clinically significant gastrointestinal conditions, including recent perforation, fistula, obstruction, or active bleeding * Active, uncontrolled, or symptomatic infection, including: * Active TB * Active hepatitis B or C * Uncontrolled HIV infection * History of immunodeficiency * Severe hypersensitivity or allergic reactions to study intervention components or monoclonal antibodies * Psychiatric illness or medical condition, including recent suicidal ideation or behavior, that may increase risk or interfere with study participation * Prior anti-angiogenic therapy or other prohibited anti-tumor or immunomodulatory therapies per protocol-specified washout periods * Use of prohibited concomitant medications, including high-dose systemic corticosteroids, certain anticoagulants, or live vaccines within protocol-specified timeframes * Recent participation in another investigational study (within 30 days or 5 half-lives, whichever is longer) * Pregnant or breastfeeding participants, or unwillingness to comply with contraception requirements

Interventions

DRUG

PF-08634404

DRUG

Chemotherapy

Interested in This Trial?

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Conditions

Small Cell Lung CancerSmall Cell Lung Cancer ( SCLC )Transformed Small Cell Lung CancerLung NeoplasmsCarcinoma, Small Cell LungSmall Cell Cancer Of The Lung

Locations

City of Hope National Medical Center

Duarte, California 91010

United States

UC San Diego Medical Center - Encinitas

Encinitas, California 92024

United States

City of Hope Lennar Foundation Cancer Center

Irvine, California 92618

United States

UC San Diego Koman Family Outpatient Pavilion

La Jolla, California 92037

United States

UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)

La Jolla, California 92037

United States

UC San Diego Moores Cancer Center

La Jolla, California 92037

United States

UC San Diego Sulpizio Cardiovascular Center

La Jolla, California 92037

United States

UC San Diego Medical Center - Bankers Hill

San Diego, California 92101

United States

UC San Diego McGrath Outpatient Pavilion - Hillcrest

San Diego, California 92103

United States

UC San Diego Medical Center- Hillcrest

San Diego, California 92103

United States

UC San Diego Medical Center - Rancho Bernardo

San Diego, California 92127

United States

UC San Diego Medical Center - Vista

Vista, California 92081

United States

Hope and Healing Clinical Research

Hinsdale, Illinois 60521

United States

Hope and Healing Clinical Research

New Lenox, Illinois 60451

United States

MSK Basking Ridge

Basking Ridge, New Jersey 07920

United States

MSK Monmouth

Middletown, New Jersey 07748

United States

MSK Bergen.

Montvale, New Jersey 07645

United States

MSK Commack

Commack, New York 11725

United States

MSK Westchester

East White Plains, New York 10604

United States

Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy

Long Island City, New York 11101

United States

Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).

New York, New York 10021

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

MSK Nassau

Uniondale, New York 11553

United States

Calvary Connery Centre

Elizabeth Vale, South Australia 5112

Australia

Hospital Beneficência Portuguesa de São Paulo

São Paulo, São Paulo 01321-001

Brazil

Hospital São Lucas da PUCRS

Porto Alegre, 90610-000

Brazil

Peking Union Medical College Hospital

Beijing, Beijing Municipality 100730

China

Fujian Cancer Hospital

Fuzhou, Fujian 350014

China

Henan Cancer Hospital

Zhengzhou, Henan 450008

China

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei 430048

China

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi 330200

China

Shanghai Chest Hospital

Shanghai, Shanghai Municipality 200030

China

The first Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang 310003

China

Centre Léon Bérard

Lyon, 69373

France

Assistance Publique Hôpitaux de Marseille - Hôpital Nord

Marseille, 13915

France

Institut Gustave Roussy

Villejuif, 94805

France

Prince of Wales Hospital

Hong Kong,

Hong Kong

Queen Mary Hospital

Hong Kong,

Hong Kong

Caritas Hospital and Institute of Health Sciences

Kottayam, Kerala 686630

India

Rajiv Gandhi Cancer Institute And Research Centre

New Delhi, National Capital Territory of Delhi 110085

India

Sheba Medical Center

Ramat Gan, HA Merkaz 5265601

Israel

Shaare Zedek Medical Center

Jerusalem, Jerusalem 9103102

Israel

Cliniche Gavazzeni S.p.A. - Humanitas Gavazzeni

Bergamo, BERGAMO 24125

Italy

IRCCS Istituto Nazionale dei Tumori Regina Elena

Roma, ROME 00144

Italy

A.O.U. San Luigi Gonzaga

Orbassano, TURIN 10043

Italy

Aichi Cancer Center Hospital

Nagoya, Aichi-ken 464-8681

Japan

Kansai Medical University Hospital

Hirakata, Osaka 573-1191

Japan

Osaka International Cancer Institute(OICI)

Osaka, Osaka 541-8567

Japan

National Cancer Center - Tsukiji Campus

Chūō, Tokyo 104-0045

Japan

Japanese Foundation for Cancer Research

Kotoku, Tokyo 135-8550

Japan

Institut Català d'Oncologia - L'Hospitalet

L'Hospitalet de Llobregat, Catalunya [cataluña] 08908

Spain

Hospital Universitario 12 de Octubre

Madrid, Madrid 28041

Spain

Hospital Universitario Virgen Del Rocio

Seville, SEVILLA 41013

Spain

National Cheng Kung University Hospital

Tainan, 704302

Taiwan

National Taiwan University Hospital

Taipei, 100

Taiwan

National Taiwan University Cancer Center (NTUCC)

Taipei, 106

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan