Carcinoma, Non-Small-Cell Lung, Lung Cancer (NSCLC), Lung Neoplasms, Carcinoma, Non-Small-Cell Lung (NSCLC), Lung Disease, Non-Small Cell Lung Cancer, Non-small Cell Lung Cancer, Non-squamous, Non-small Cell Lung Cancer, Squamous
Conditions
Keywords
early stage non small cell lung cancer, NSCLC, adjuvant NSCLC, locally advanced non small cell lung cancer, resectable NSCLC, unresectable NSCLC, neoadjuvant NSCLC, consolidation NSCLC, squamous NSCLC, non-squamous NSCLC
Brief summary
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.
Interventions
BIOLOGICALPF-08634404
Concentrate for solution for infusion
Injection for intravenous use
Injection for intravenous use
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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. * Unresolved toxicities from prior anti-tumor therapy, that did not recover to NCI CTCAE v5.0 Grade 0 or 1. * 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. * History of allogeneic organ / hematopoietic stem cell transplantation. * Participants with any of the following respiratory conditions: * Evidence of noninfectious or drug-induced interstitial lung disease (ILD) or pneumonitis * Grade ≥3 pulmonary disease unrelated to underlying malignancy * History of uncontrolled comorbidities within 6 months prior to the first dose including uncontrolled cardiac and cerebrovascular conditions, hypertension, diabetes, significant vascular disease or arterial/severe venous thromboembolic events. * Major surgery \< 4 weeks or minor surgery \< 3 days prior to first dose of study intervention. * History of severe bleeding tendency or coagulation dysfunction * 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 participants positive for active HIV, hepatitis B virus (HBV), or Hepatitis C virus (HCV). * Participants with history of immunodeficiency * Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior (in the past 5 years) or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study. * Breastfeeding participants, participants of childbearing potential, and male participants who are unwilling to follow contraceptive measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Through 90 days after the last dose of study intervention (Part A only: or 90 days after surgery, whichever is later) | 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 | Up to approximately 6 months after first dose | 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 | Up to approximately 6 months after first dose | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Major Pathological Response (MPR) rate per IASLC guidelines as assessed by central pathology review | Up to approximately 6 months after first dose | 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 | Up to approximately 6 months after first dose | 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 | Up to approximately 6 months after first dose | 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 | Up to approximately 5 years | 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. |
| Part A: Objective Response Rate (ORR) per RECIST v1.1 as assessed by investigator at the completion of neoadjuvant therapy, prior to surgery | Up to approximately 5 years | ORR is defined as the proportion of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST v1.1. |
| Part B: Disease Free Survival (DFS) per RECIST v1.1 as assessed by investigator | Up to approximately 5 years | DFS is defined as time from the date of first dose to the date of first documented disease progression or recurrence per RECIST v1.1 as assessed by investigator or death due to any cause, whichever occurs first |
| Part C: Confirmed ORR per RECIST v1.1 as assessed by investigator | Up to approximately 5 years | Confirmed ORR is defined as the proportion of participants in the analysis population having a best overall response (BOR) of confirmed CR or confirmed PR according to RECIST v1.1 as assessed by investigator. |
| Part C: Progression Free Survival (PFS) per RECIST v1.1 as assessed by investigator | Up to approximately 5 years | PFS is defined as the time from the date of first dose to the date of the first documentation of objective Progression Disease (PD) assessed by investigator per RECIST v1.1, or death due to any cause, whichever occurs first |
| Overall Survival (OS) | Up to approximately 5 years | OS is defined as the time from the date of randomization to the date of death due to any cause. OS is secondary outcome measure in Phase 2 portion of the study. |
| Rate of circulating tumor DNA (ctDNA) reduction or clearance | Part A: Up to 18 months, Part B and Part C: Up to 37 days after the last dose of treatment | Reduction in ctDNA is defined as a decrease in ctDNA burden from baseline to a specified on-treatment time point. ctDNA clearance is defined as a 100% reduction in ctDNA burden. |
| Number of participants with Laboratory abnormalities | Through 90 days after the last dose of study intervention (Part A only: or 90 days after surgery, whichever is later) | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0). |
| Pharmacokinetics: Serum concentrations of PF-086344 | Up to 37 days after the last dose of treatment, prior to surgery | — |
| Incidence of antidrug antibody against PF-08634404 | Up to 37 days after the last dose of treatment, prior to surgery | — |
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed