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
Participants with known EGFR and ALK AGAs; documented negative results for EGFR and ALK AGAs are required for participants with non-squamous histology.
Participants with CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression.
Participants with clinically significant risk of hemorrhage or fistula are excluded.
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.
Parallel
PF-08634404
Biological/VaccineConcentrate for solution for infusion
Chemotherapy Regimen 1
DrugInjection for intravenous use
Chemotherapy Regimen 2
DrugInjection for intravenous use
Number of Participants With Adverse Events (AEs)
AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s).
Part A: Surgical Feasibility Rate
Surgical Feasibility rate is defined by the proportion of participants undergoing surgery and the proportion of participants with wound complications after surgery.
Part A: Pathological Complete Response (pCR) rate per International Association for the Study of Lung Cancer (IASLC) guidelines as assessed by central pathology review
pCR rate by central pathology review is defined as the proportion of participants having pCR as assessed by central pathologist. pCR is defined as the absence of residual tumor in surgical specimens
Part A: Major Pathological Response (MPR) rate per IASLC guidelines as assessed by central pathology review
MPR rate by central pathology review is defined as the proportion of participants having MPR as assessed by central pathologist or investigator respectively. MPR is defined as ≤10% residual tumor in surgical specimens.
Part A: pCR rate per IASLC guidelines as assessed by investigator
pCR rate by investigator is defined as the proportion of participants having pCR as assessed by investigator. pCR is defined as the absence of residual tumor in surgical specimens.
Part A: MPR rate per IASLC guidelines as assessed by investigator
MPR rate by investigator is defined as the proportion of participants having MPR as assessed by central pathologist or investigator respectively. MPR is defined as ≤10% residual tumor in surgical specimens.
Part A: Event Free Survival (EFS) per RECIST v1.1 as assessed by investigator
EFS is defined as time from the date of first dose to the first occurrence of disease progression precluding surgery, inability to resect the tumor, disease progression or recurrence after surgery per RECIST v1.1 as assessed by investigator, or death due to any cause.
