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
This study is being done to learn more about a new medicine called PF-08634404. The study team wants to understand how well it works when given alone or with chemotherapy. The study is for adults with early stage or locally advanced non-small cell lung cancer (NSCLC) that may or may not be removable with surgery. The study is seeking participants who: * Are aged 18 years or older * Have either: * Early-stage or locally advanced (Stage II or IIIA/B) NSCLC and are a candidate for neoadjuvant therapy, followed by surgical removal of the tumor. Neoadjuvant therapy is a treatment given as a first step to shrink the tumor before surgery. * Early-stage or locally advanced (Stage II or IIIA/B) NSCLC and are a candidate for adjuvant therapy and did not achieve a pathological complete response (pCR) from approved treatment that was administered before surgery. Adjuvant therapy is an additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. pCR is defined as absence of viable tumor in all surgically removed samples. * Locally advanced (Stage III) NSCLC that may not be removable with surgery, was treated with concurrent chemoradiotherapy (cCRT), and is a candidate for additional treatment, otherwise known as consolidation therapy. cCRT is chemotherapy and radiation given simultaneously. * Be in good physical condition and have healthy organs based on medical tests. * Do not have known actionable changes in DNA The study has 3 parts and each participant will be assigned to one part by their doctor based on their disease diagnosis: * Part A will test PF-08634404 given with chemotherapy in the neoadjuvant setting, followed by surgery. * Part B will test PF-08634404 alone in adults who already were treated with neoadjuvant chemo-immunotherapy, underwent surgery, and did not achieve pCR per tumor tissue pathology analysis. Neoadjuvant chemo-immunotherapy refers to the combination of chemotherapy with immunotherapy per local standard-of-care, given before surgical removal of the tumor. * Part C will test PF-08634404 alone in adults with unresectable disease who received cCRT and did not have progressive disease. Progressive disease refers to a condition that grows, spreads, or worsens. All treatments will be done at clinical study sites, where a trained medical team will monitor adults during and after each visit.
• 18 years of age or older at screening.
• Have tumor tissue available, either paraffin block or slides from a core, excisional or fine needle biopsy
• PD-L1 status available based on local testing results
• Adequate organ function
• Eastern Cooperative Oncology Group performance status (ECOG) score of 0 or 1
• Part A only: 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.
• Part B only: 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.
• Part C only: 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 and achieved SD or better per RECIST 1.1.