2025-524686-24-00招募中2 期
C6461014 - A Phase 2 Interventional Study of PF-08634404 in Combination with Chemotherapy in Participants with Previously Untreated Transformed Small Cell Lung Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Pfizer Inc.
- 入组人数
- 15
- 试验地点
- 12
- 主要终点
- Confirmed ORR as assessed by investigator based on RECIST v1.1
研究概览
简要总结
•To determine the antitumor activity of PF-08634404 in combination with chemotherapy •To evaluate safety and tolerability of PF-08634404 in combination with chemotherapy
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening.
- •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). Patients with transformed SCLC after therapy for NSCLC with mutations other than EGFR will be excluded. Participants with a history of NSCLC without AGAs or squamous histology will also be excluded.
- •Participants have not received systemic therapy for T-SCLC. Participants who received a single cycle of chemotherapy (without immune checkpoint inhibitors) prior to screening for the management of life-threatening T-SCLC (such as superior vena cava syndrome but no cord compression) may be eligible.
- •Have at least one measurable lesion as the target lesion based on RECIST v1.
- •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 target lesion, evidence-based radiology must be provided to demonstrate disease progression (a single bone metastasis or a single central nervous system metastasis should not be considered as a measurable lesion).
- •Have sufficient tumor tissue from the diagnosis of transformed SCLC 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 notification to the medical monitor. c) In addition to required T-SCLC tissue, submission of archival NSCLC tissue taken prior to diagnosis of T-SCLC is optional but highly encouraged.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Have a minimum life expectancy of >12 weeks.
- •Have adequate organ function, as defined below: a) Participants must meet the hematologic criteria below in Table 5 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.
- •The participant must provide written informed consent.
排除标准
- •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. 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
- •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.
- •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.
- •Participants with pleural effusion, pericardial effusion, or ascites that are clinically symptomatic or require repeated drainage (once a month or more frequently).
- •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).
- •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;
- •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 enrollment. 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;
- •Participants with history of immunodeficiency
- •Known to have a history of a severe allergy to any component of the study intervention, or a history of severe allergic reaction to chimeric or humanized antibody;
- •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.
- •Other circumstances that may increase the study-related risks or interfere with interpretation of the study results, in the opinion of the investigator.
- •Leptomeningeal disease
- •Previous systemic anti-tumor therapy including: a) Anti-angiogenic agents targeting VEGF, its receptor or other specific molecules involved in angiogenesis. b) Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received. c) Palliative local therapy within 2 weeks before the first dose; d) Non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, excluding IL-11 for thrombocytopenia treatment) within 2 weeks before the first dose. Note: Previous systemic anti-tumor therapy for NSCLC with chemotherapy and immunotherapy is allowed. Participant must have failed TKI(s) for EGFR mutant NSCLC.
- •For participants who have been previously exposed to PD-(L)-1 inhibitors: a) History of Grade 3 or higher irAEs (excluding endocrine system-related irAEs) caused by immunotherapy, irAEs leading to permanent discontinuation of treatment, Grade 2 immune-related cardiotoxicity, or irAEs of any grade affecting the nervous system or eyes. b) All adverse events from prior immunotherapy have not completely resolved or have not improved to Grade 1 before screening for this study. Participants with endocrine system-related adverse events Grade ≥2 may be enrolled if they are stable on appropriate replacement therapy and asymptomatic. c) History of adverse events requiring treatment with immunosuppressants other than corticosteroids, or recurrence of adverse events during prior immunotherapy necessitating systemic corticosteroid therapy again.
- •Prior and concomitant therapy: a) Use of therapeutic oral or parenteral anticoagulants within 10 days prior to the first dose (excluding use of anticoagulants as secondary prophylaxis); note: Full-dose oral or parenteral anticoagulants are permitted if the INR or aPTT is within the therapeutic range and the participant has been on a stable dose of anticoagulants for at least 2 weeks prior to the first dose. Prophylactic use of anticoagulants for secondary prophylaxis is permitted. b) Use of chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole, clopidogrel, or similar agents within 7 days prior to enrollment. Once-daily aspirin use (maximum dose 325 mg/day) is permitted. c) Use of any live or attenuated live vaccine within 4 weeks prior to the first dose, or planned vaccination of any live or attenuated live vaccine during the study. d) Current use of a high-dose systemic corticosteroids (>10 mg daily prednisone or equivalent) or other immune suppressant or has a condition requiring a chronic high-dose steroid or immune suppressant. e) Use of any prohibited concomitant medication(s) within 21 days of the first dose of study intervention or unwillingness or inability to use a required concomitant medication(s). Refer to Section 6.
- •Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.
- •Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
- •Breastfeeding participants; participants of childbearing potential and male participants who are unwilling to follow pregnancy measures.
- •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 enrollment must exclude major airway or blood vessel invasion by tumor.
- •Participants with any history of another malignancy (other than NSCLC) 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.
- •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 the medical monitor will be informed. Participants with long-term toxicity from radiotherapy that is deemed irreversible by the investigator may be enrolled in the study Information should be provided to the medical monitor before proceeding.
- •History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- •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).
- •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 the medical monitor is informed. 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).
- •History of uncontrolled comorbidities within 6 months prior to the first dose including but not limited to the following: 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)
研究组 & 干预措施
CARBOPLATIN
Test
干预措施: CARBOPLATIN (Drug)
ETOPOSIDE
Test
干预措施: ETOPOSIDE (Drug)
PF-08634404
Test
干预措施: PF-08634404 (Drug)
结局指标
主要结局
Confirmed ORR as assessed by investigator based on RECIST v1.1
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.
AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
次要结局
- DOR as assessed by investigator based on RECIST v1.1
- PFS as assessed by investigator based on RECIST v1.1
- OS
- Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
- Predose and postdose concentrations of PF-08634404.
- Incidence of ADA against PF-08634404.
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (12)
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