AN INTERVENTIONAL PHASE 3, DOUBLE-BLIND, RANDOMIZED STUDY TO EVALUATE EFFICACY AND SAFETY OF PF-08634404 IN COMBINATION WITH CHEMOTHERAPY VERSUS PEMBROLIZUMAB IN COMBINATION WITH CHEMOTHERAPY IN ADULT PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER

Plain English Summary

Symbiotic-Lung-01 : A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer is a Phase 3 clinical trial sponsored by Pfizer studying Advanced Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Carcinoma, Non-Small-Cell Lung (NSCLC), Metastatic Non Small Cell Lung Cancer, Lung Cancer. This trial tests if a new drug, PF-08634404, combined with chemotherapy, is more effective than the current standard treatment (pembrolizumab with chemotherapy) for advanced lung cancer. It is for adults with non-small cell lung cancer (NSCLC) that is locally advanced or has spread to other parts of the body. Participants will receive one of two treatment combinations through IV infusions, assigned randomly. This involves regular clinic visits for treatment and monitoring. The current standard treatment for this type of lung cancer is pembrolizumab plus chemotherapy. The trial aims to enroll 1410 participants.

Official Summary

This study is being done to find out if a new medicine called PF-08634404, when given with chemotherapy, works better than the present standard treatment (pembrolizumab with chemotherapy) for adults with a type of lung cancer called non-small cell lung cancer (NSCLC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body. To join the study, participants must meet the following conditions: * Be 18 years or older. * Have locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC. * Is not a candidate for complete surgical resection or curative chemoradiotherapy. * Do not have known actionable genomic alterations * Be treatment naïve for advanced or metastatic disease Participants in this study will be assigned to two different parts of the study depending on their type of tumor: participants with squamous NSCLC will be assigned to Part 1, while participants with non-squamous NSCLC will be assigned to Part 2. Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups in a blinded fashion: * Part 1 - Arm A or Part 2 - Arm C (Experimental Group): Will receive a new study medicine called PF-08634404 along with a kind of chemotherapy specific to the type of tumor. * Part 1 - Arm B or Part 2 - Arm D (Control Group): Will receive an approved medicine called pembrolizumab along with a kind of chemotherapy specific to the type of tumor. Participants will receive their assigned treatment through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, participants will receive PF-08634404 or Pembrolizumab in combination with chemotherapy followed by maintenance with either PF-08634404 or Pembrolizumab monotherapy (Part 1) or PF-08634404 or Pembrolizumab in combination with a chemotherapeutic drug (Part 2). Participants will continue receiving treatment if it is helping and not experiencing s

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with Stage IIIB/IIIC or Stage IV non-small cell lung cancer. Patients must not be candidates for surgery or curative chemoradiotherapy and must not have received prior treatment for advanced or metastatic disease. Individuals with certain genetic alterations in their tumors for which other treatments are available cannot participate. Patients with active brain metastases or certain other serious health conditions may not be eligible. This trial is studying Advanced Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Carcinoma, Non-Small-Cell Lung (NSCLC), Metastatic Non Small Cell Lung Cancer, Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The trial will measure how long patients live (Overall Survival) and how long their cancer stays under control without getting worse (Progression Free Survival) to see if the new drug combination is m The specific primary outcome measures are: Overall Survival (Approximately 39 months); Progression Free Survival (PFS) assessed by blinded independent central review (BICR) (Approximately 32 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to find a better treatment option for patients with advanced non-small cell lung cancer, addressing the need for more effective therapies when the cancer has spread. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Advanced Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Carcinoma, Non-Small-Cell Lung (NSCLC), Metastatic Non Small Cell Lung Cancer, Lung Cancer, where improved treatment options are needed.

Investor Insight

This Phase 3 trial sponsored by Pfizer, a major pharmaceutical company, investigates a novel combination therapy for a large market of lung cancer patients, suggesting a significant potential if succe Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1410 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of both treatment arms, including the new drug PF-08634404. Be prepared for regular IV infusions and follow-up appointments for monitoring your health and cancer progression. Understand that you will be randomly assigned to one of the two treatment groups, and your participation will be closely monitored. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 1,410 participants

Interventions

• BIOLOGICAL: PF-08634404 — Solution for infusion
• BIOLOGICAL: Pembrolizumab — Injection for IV use
• DRUG: Chemotherapy Regimen 1 — Injection for IV use
• DRUG: Chemotherapy Regimen 2 — Injection for IV use

Primary Outcomes

• Overall Survival (Approximately 39 months)
• Progression Free Survival (PFS) assessed by blinded independent central review (BICR) (Approximately 32 months)

Secondary Outcomes

• Confirmed objective response rate (ORR) using RECIST v1.1 as assessed by BICR (Approximately 32 months)
• Progression Free Survival as assessed by Investigator (Approximately 32 months)
• Confirmed ORR using RECIST v1.1 as assessed by investigator (Approximately 32 months)
• Duration of Response (DoR) as assessed by BICR (Approximately 32 months)
• Duration of Response (DoR) as assessed by Investigator (Approximately 32 months)

Full Eligibility Criteria

Inclusion Criteria:

* 18 years of age or older at screening.
* Have pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV)squamous or non-squamous NSCLC and not be a candidate for complete surgical resection and curative concurrent/sequential chemoradiotherapy (according to the 9th edition of the Union for International Cancer Control and American Joint Committee on Cancer lung cancer Tumor, lymph nodes, metastasis (TNM) staging system).
* 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
* Measurable disease based on RECIST v1.1 per investigator.
* Eastern Cooperative Oncology Group performance status (ECOG) score of 0 or 1
* Expected survival ≥12 weeks

Exclusion Criteria:

* Participants with known actionable genomic alteration (AGAs), including estimated glomerular filtration rate (EGFR), anaplastic lymphoma kinase (ALK), Repressor of Silencing 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), rearranged during transfection (RET), and mesenchymal-epithelial transition (MET), for which there are available first-line therapies per local standard-of-care (SOC) are ineligible. Documented negative results for EGFR, ALK, and ROS1 AGAs are required for participants with non-squamous histology.
* Known active CNS lesions are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be eligible. Clinically inactive brain metastases of longest diameter \< 1 cm are permitted.
* 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.
* Previous systemic anti-tumor therapy including:

  1. Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.
  2. Previous treatment with immunotherapy
  3. Prior radiotherapy \> 30 Gy to the lung \< 6 months of first dose of study intervention
  4. Palliative local therapy \< 2 weeks before the first dose of study intervention;
  5. Non-specific immunomodulatory therapy \< 2 weeks before the first dose.
  6. Prior systemic anti-angiogenic therapy
* Prior immune-related AE that led to anti-PD-(L)1 treatment discontinuation, adverse events from prior immunotherapy not improved to Grade 1 before screening, or required treatment with systemic immunosuppressive therapy.
* Prior and concomitant therapy:

  1. therapeutic oral or parenteral anticoagulants or thrombolytic agents \< 10 days to the first dose.
  2. chronic antiplatelet therapy \<7 days to randomization.
  3. live or attenuated live vaccine \< 4 weeks to the first dose.
  4. current high-dose systemic corticosteroids.
  5. prohibited concomitant medication(s) \< 21 days to the first dose.
* Breastfeeding participants, participants of childbearing potential, and male participants who are unwilling to follow contraceptive measures.

Trial Locations

• Ironwood Cancer & Research Centers, Chandler, Arizona, United States
• Ironwood Cancer & Research Centers, Gilbert, Arizona, United States
• Ironwood Cancer & Research Centers, Glendale, Arizona, United States
• Ironwood Cancer & Research Centers, Goodyear, Arizona, United States
• Ironwood Cancer & Research Centers, Mesa, Arizona, United States
• Ironwood Cancer & Research Centers, Mesa, Arizona, United States
• Ironwood Cancer & Research Centers, Phoenix, Arizona, United States
• Ironwood Cancer & Research Centers, Scottsdale, Arizona, United States
• Highlands Oncology Group, Fayetteville, Arkansas, United States
• Highlands Oncology Group, Rogers, Arkansas, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• Metastatic Lung Cancer
• Advanced Lung Cancer
• Lung Carcinoma
• Squamous Cell Lung Cancer
• Non-Squamous Cell Lung Cancer
• Chemotherapy
• Immunotherapy
• Targeted Therapy
• Oncology

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