Symbiotic-Lung-10: A Study to Learn About PF-08634404 Alone or in Combination in Early-stage or Locally Advanced NSCLC

Official title

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

Overview

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

• Biological PF-08634404
  Concentrate for solution for infusion
• Drug Chemotherapy Regimen 1
  Injection for intravenous use
• Drug Chemotherapy Regimen 2
  Injection for intravenous use

Primary outcome measures

• Number of Participants With Adverse Events (AEs) [Time frame: Through 90 days after the last dose of study intervention (Part A only: or 90 days after surgery, whichever is later)]
• Part A: Surgical Feasibility Rate [Time frame: Up to approximately 6 months after first dose]
• Part A: Pathological Complete Response (pCR) rate per International Association for the Study of Lung Cancer (IASLC) guidelines as assessed by central pathology review [Time frame: Up to approximately 6 months after first dose]

Secondary outcome measures (12)

• Part A: Major Pathological Response (MPR) rate per IASLC guidelines as assessed by central pathology review [Time frame: Up to approximately 6 months after first dose]
• Part A: pCR rate per IASLC guidelines as assessed by investigator [Time frame: Up to approximately 6 months after first dose]
• Part A: MPR rate per IASLC guidelines as assessed by investigator [Time frame: Up to approximately 6 months after first dose]
• Part A: Event Free Survival (EFS) per RECIST v1.1 as assessed by investigator [Time frame: Up to approximately 5 years]
• Part A: Objective Response Rate (ORR) per RECIST v1.1 as assessed by investigator at the completion of neoadjuvant therapy, prior to surgery [Time frame: Up to approximately 5 years]
• Part B: Disease Free Survival (DFS) per RECIST v1.1 as assessed by investigator [Time frame: Up to approximately 5 years]
• Part C: Confirmed ORR per RECIST v1.1 as assessed by investigator [Time frame: Up to approximately 5 years]
• Part C: Progression Free Survival (PFS) per RECIST v1.1 as assessed by investigator [Time frame: Up to approximately 5 years]
• Overall Survival (OS) [Time frame: Up to approximately 5 years]
• Rate of circulating tumor DNA (ctDNA) reduction or clearance [Time frame: Part A: Up to 18 months, Part B and Part C: Up to 37 days after the last dose of treatment]
• Number of participants with Laboratory abnormalities [Time frame: Through 90 days after the last dose of study intervention (Part A only: or 90 days after surgery, whichever is later)]
• Pharmacokinetics: Serum concentrations of PF-086344 [Time frame: Up to 37 days after the last dose of treatment, prior to surgery]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Clearview Cancer Institute (Crestwood) — Huntsville
• Clearview Cancer Institute — Huntsville
• University Cancer & Blood Center, LLC — Athens
• Hope and Healing Clinical Research — Hinsdale
• Hope and Healing Clinical Research — New Lenox
• Cancer Partners of Nebraska — Lincoln
• University of Tennessee Medical Center — Knoxville

Puerto Rico · 5 centers

• Pan American Center for Oncology Trials, LLC - Bayamón Office — Bayamón
• Pan American Center for Oncology Trials, LLC - Manati Office — Manati
• Pan American Center for Oncology Trials, LLC - Ponce Office — Ponce
• Hospital Oncologico Dr. Isaac Gonzalez Martinez — Rio Piedras
• Pan American Center for Oncology Trials, LLC - Ciudadela Office — San Juan

China · 1 center

• Guangdong Provincial People's Hospital — Guangzhou

Taiwan · 1 center

• Taipei Medical University Hospital — Taipei

Identifiers

NCT: NCT07489066 · C6461010 · 2025-524825-42-00 · Symbiotic-Lung-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗