2025-524825-42-00招募中2 期
C6461010 - An Interventional, Open-Label, Phase 2 Study to Investigate the Safety and Efficacy of PF-08634404 Monotherapy or in Combination in Adult Participants with Early-Stage Resectable or Locally Advanced Unresectable Non-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
- 33
- 试验地点
- 24
- 主要终点
- PART A: • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.; • Proportion of participants undergoing surgery;• Proportion of participants with wound complications after surgery; • pCR rate per IASLC guidelines as assessed by central pathology review
研究概览
简要总结
PART A:• To evaluate safety and tolerability of PF-08634404 + platinum doublet chemotherapy as neoadjuvant therapy; • To assess the surgical feasibility rate in participants receiving PF-08634404 + platinum doublet chemotherapy as neoadjuvant therapy; • To evaluate pCR rate in participants receiving PF-08634404 + platinum doublet chemotherapy as neoadjuvant therapy; PART B: • To evaluate safety and tolerability of PF 08634404 monotherapy as adjuvant therapy; PART C: • To evaluate safety and tolerability of PF-08634404 monotherapy as consolidation therapy
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ 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. • 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 pregnancy test (minimum sensitivity 25 mIU/mL or equivalent quantitative assay) result at Screening and within 72 hours prior to the first dose of study treatment. Participants with false positive results and documented verification that the participant is not pregnant are eligible for participation.
- •PART B: PD-L1 status available based on local testing results
- •PART C: Participants must have pathologically confirmed LA, unresectable (Stage III) squamous or non-squamous NSCLC (according to the 9th edition of the Union for International Cancer Control and American Joint Committee on Cancer lung cancer TNM staging system) and have received ≥ 60 Gy of radiation and ≥ 2 cycles of definitive, platinum-based concurrent chemotherapy within [CCI] before first dose and achieved SD or better per RECIST 1.
- •The platinum-based chemotherapy regimen may contain one of the following agents: etoposide, vinblastine, a taxane (paclitaxel), or pemetrexed, according to the local standard of care regimens. Approximately [CCI]% of participants should have squamous histology. • Mixed-type tumors will be classified by pathological type based on the predominant cell type. • Must not have small cell elements present. • Large cell neuroendocrine carcinoma is excluded.
- •PART C: PD-L1 status available based on local testing results • Enrollment of participants with TPS < 1% will be capped at 30%.
- •ECOG PS score of 0 or
- •Expected survival ≥12 weeks.
- •Adequate organ function determined by meeting the following criteria within 7 days prior to first study intervention administration: • 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.
- •The participant must provide written informed consent.
- •PART A: Submission of sufficient tumor tissue is required, if available. Tissue samples may be submitted as 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) • Archival specimen from the most recent biopsy before the start of study intervention. See Central Laboratory Manual for tissue specifications, handling, and shipping instructions.
- •PART A: Participants must have newly diagnosed, previously untreated, pathologically confirmed early-stage or LA (Stage II or IIIA/B), squamous or non-squamous NSCLC (according to the 9th edition of the Union for International Cancer Control and American Joint Committee on Cancer lung cancer TNM staging system) with disease that is considered resectable, as assessed by a multidisciplinary evaluation, which must include a thoracic surgeon who performs lung cancer surgery as a prominent part of his/her practice. The participant must be a candidate for neoadjuvant therapy followed by complete surgical resection. • Mixed-type tumors will be classified by pathological type based on the predominant cell type. • Must not have small cell elements present. • Large cell neuroendocrine carcinoma is excluded.
- •PART A: PD-L1 status available based on local testing results
- •PART B: Participants must have pathologically confirmed early-stage or LA (Stage II or IIIA/B), squamous or non-squamous NSCLC (according to the 9th edition of the Union for International Cancer Control and American Joint Committee on Cancer lung cancer TNM staging system) and have undergone complete surgical resection. The participant must be considered a candidate for adjuvant therapy and must not have achieved pCR with SOC neoadjuvant chemo-immunotherapy. [CCI]
排除标准
- •Participants with known EGFR and ALK AGAs; documented negative results for EGFR and ALK AGAs are required for participants with non-squamous histology.
- •Major surgery or severe trauma less than 4 weeks prior to the first dose or planned major surgery (other than surgical procedures related to NSCLC) 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.
- •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 recurrent epistaxis (excluding minor nosebleeds and blood-tinged nasal discharge).
- •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 (see Section 10.5). c. Known to be 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.
- •Participants with CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression
- •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.
- •Unresolved toxicities from prior antitumor 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; the medical monitor should be informed. Participants with longterm toxicity from radiotherapy that is deemed irreversible by the investigator may be enrolled; the medical monitor should be informed.
- •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 8), 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 7b). d. Participants with Sjögren’s syndrome are allowed (if not excluded per exclusion criterion 7b).
- •Participants with any of the following respiratory conditions: a. Evidence of non-infectious or drug induced ILD or pneumonitis that: i. Was previously diagnosed and was managed with parenteral steroids for any duration or oral steroids for >6 weeks, or ii. Had onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or iii. Is currently diagnosed and managed with systemic therapy, or iv. Is suspected on radiologic imaging at screening. v. 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. Any Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to: i. 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. ii. Severe chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids. iii. 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 8k. iv. 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: 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
- •Baseline QTcF interval > 480 msec a. 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 must be overread by an investigator physician experienced in reading ECGs before excluding participants.
研究组 & 干预措施
CARBOPLATIN
Test
干预措施: CARBOPLATIN (Drug)
PF-08634404
Test
干预措施: PF-08634404 (Drug)
PEMETREXED
Test
干预措施: PEMETREXED (Drug)
PACLITAXEL
Test
干预措施: PACLITAXEL (Drug)
结局指标
主要结局
PART A: • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.; • Proportion of participants undergoing surgery;• Proportion of participants with wound complications after surgery; • pCR rate per IASLC guidelines as assessed by central pathology review
PART A: • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.; • Proportion of participants undergoing surgery;• Proportion of participants with wound complications after surgery; • pCR rate per IASLC guidelines as assessed by central pathology review
PART B: • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
PART B: • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
PART C: • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
PART C: • 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
- PART B: • Predose and/or postdose concentrations of PF 08634404.
- PART B: • Incidence of ADA against PF 08634404.
- PART A: • Rate of ctDNA reduction or clearance
- PART A: • MPR rate per IASLC guidelines as assessed by central pathology review; • pCR rate per IASLC guidelines as assessed by investigator; • MPR rate per IASLC guidelines as assessed by investigator
- PART A: • EFS per RECIST v1.1 as assessed by investigator; • OS; • ORR per RECIST v1.1 as assessed by investigator at the completion of neoadjuvant therapy, prior to surgery
- PART A: • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0)
- PART A: • Predose and/or postdose concentrations of PF 08634404
- PART A: • Incidence of ADA against PF 08634404.
- PART B: • DFS per RECIST v1.1 as assessed by investigator; • OS
- PART B: • Rate of ctDNA reduction or clearance
- PART B: • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0)
- PART C: • Confirmed ORR per RECIST v1.1 as assessed by investigator; • PFS per RECIST v1.1 as assessed by investigator; • OS
- PART C: • Rate of ctDNA reduction or clearance
- PART C: • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0)
- PART C: • Predose and/or postdose concentrations of PF 08634404
- PART C: • Incidence of ADA against PF-08634404
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (24)
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