AN INTERVENTIONAL OPEN-LABEL PHASE 1B/2 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PRELIMINARY EFFICACY OF PF-08634404 IN COMBINATION WITH DIFFERENT ANTICANCER AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

Study Identifier:
C6461020
CT.gov Identifier:
NCT07227298
EudraCT Identifier:
202552352640
EU Trial (CTIS) Number:
2025-523526-40-00
Study Contact Information:
(210) 593-5651 or [email protected]
Will Be Recruiting

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Study Summary

This study is being done to learn more about a new medicine called PF-08634404 and how it works when used with other cancer medicines in people who have advanced solid tumors. An advanced solid tumor is a type of cancer that has spread beyond its original location and cannot be removed by surgery or cured with standard treatments.

To join in the study, participants must:

  • Be 18 years or older
  • Participants with advanced non-small cell lung cancer (NSCLC), a type of lung cancer that has spread

The study will look at:

  • Whether PF-08634404 is safe to use with other cancer medicines.
  • What side effects may happen. A side effect is anything the medicine does to your body that is not part of treating your disease.
  • Whether the combination of PF-08634404 and other cancer medicines can help treat solid tumors.

The study has different parts, each testing PF-08634404 with a different cancer medicine:

  • Part A will test PF-08634404 with a medicine called sigvotatug vedotin.
  • Part B of the study will look at how well the new medicine PF-08634404 works when used together with another medicine.

Participants will receive the study medicines through an intravenous (IV) infusion (injected into the vein) at the study clinic. All treatments will take place at clinical trial sites, where trained medical staff will monitor participants during and after each visit.

This study aimed to evaluate whether combination therapy with different ADCs (including Sigvotatug Vedotin and PF-08046054) as first-line treatment could improve clinical outcomes in study participants with squamous and non-squamous LA/M NSCLC without driver gene mutations (AGA).

Main objective

Phase 1 Safety Run-In: To evaluate safety and tolerability of PF-08634404 + SV or PF-08634404 + PF-08046054 Phase 2 Dose Optimization and Dose Expansion: To evaluate antitumor efficacy in PF-08634404 + SV or PF-08634404 + PF-08046054 To evaluate safety and tolerability of PF-08634404 + SV or PF-08634404 + PF-08046054 To identify a recommended dose of PF-08634404 + SV or PF-08634404 + PF-08046054

Main objective

This study aims to evaluate whether combining PF-08634404 with various ADCs (including Sigvotatug Vedotin and PF-08046054) as first-line treatment for squamous and non-squamous LA/M NSCLC patients without driver gene mutations (AGA) can improve clinical outcomes.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Non-Small Cell Lung Cancer
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Will Be Recruiting

Requirements information
Inclusion criteria
  • * Pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC and are not a candidate for complete surgical resection and curative concurrent/sequential chemoradiotherapy * PD-L1 status available * Part B only: PD-L1 ≥ TPS 1% * Measurable disease based on RECIST v1.1 per investigator. * Eastern Cooperative Oncology Group performance status of 0 or 1. * Adequate organ function At the time of screening, applicants must be ≥18 years old (or the minimum consent Age as determined by local regulations).
  • Study participants must meet the following criteria: pathologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) squamous or non-squamous NSCLC, and not suitable for complete surgical resection and radical concurrent/sequential chemoradiotherapy.
  • A PD-L1 expression report based on local testing results is required. Part B only: PD-L1 ≥ TPS 1%
  • Researchers used RECIST v1.1 to determine that lesions were measurable.
  • The ECOG PS score is 0 or 1.
  • Organ function was confirmed to be adequate after assessment.
  • 1At the time of screening, ≥ must be 18 years old (or the minimum age of consent determined by local regulations).2Study participants must meet the following criteria: pathologically confirmed to be locally advanced (stage IIIB/IIIC) or metastatic (stage IV) squamous or non-squamous NSCLC, and not suitable for complete surgical resection or radical simultaneous/sequential chemoradiotherapy.3A PD-L1 expression report based on local test results must be provided. Part B only: PD-L1 ≥ 1% TPS4Researchers identified measurable lesions based on RECIST v1.1.5ECOG PS score is 0 or 1.6Assessment confirms adequate organ function
  • Inclusion Criteria:
  • *Pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC and are not a candidate for complete surgical resection and curative concurrent/sequential chemoradiotherapy
  • *PD-L1 status available
  • *Part B only: PD-L1 >= TPS 1%
  • *Measurable disease based on RECIST v1.1 per investigator.
  • *Eastern Cooperative Oncology Group performance status of 0 or 1.
  • *Adequate organ function
Exclusion criteria
  • Participants with known AGAs including EGFR, ALK and ROS1, NTRK, BRAF, and MET * 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 * Known active CNS lesions, including brainstem, meningeal, or spinal cord metastases or compression * Leptomeningeal disease * Active autoimmune diseases requiring systemic treatment within the past 2 years * Previous systemic anti-tumor therapy for locally advanced, unresectable, or metastatic NSCLC * Previous treatment with immunotherapy (exception is (neo)adjuvant anti-PD-(L)1), ADCs containing MMAE payload, systemic anti-angiogenic therapy, or prior radiotherapy to the lung within 6 months of first dose of study intervention
  • AGAs (including EGFR, ALK, ROS1, NTRK, BRAF, RET, and MET) exist.
  • Research participants with active CNS lesions (including brainstem/meningeal/spinal cord metastases or compression) should be excluded.
  • Research participants with leptomeningeal metastases.
  • Clinically significant risk of bleeding or fistula.
  • Study participants had a history of other malignancies within 3 years prior to the first administration of the study treatment intervention, or evidence of any residual lesions in a previously diagnosed malignancy.
  • Participants in studies of active autoimmune diseases that require systemic treatment within the past two years.
  • Prior systemic antitumor therapy, including: a) prior systemic therapy for locally advanced, unresectable, or metastatic NSCLC; b) prior immunotherapy, excluding neoadjuvant anti-PD-(L)1 therapy; c) prior treatment with an ADC containing MMAE payload; d) prior lung radiotherapy within 6 months prior to the first dose of the study treatment intervention; e) prior systemic anti-angiogenic therapy (including but not limited to bevacizumab and its biosimilars, endostatin, small molecule TKIs, and ramoximab).
  • 1存在 AGA(包括 EGFR、ALK、ROS1、NTRK、BRAF、RET 及 MET)2Study participants with active CNS lesions (including brainstem/meningeal/spinal cord metastasis or compression) should be excluded.3There were study participants with pia mater metastasis.4Clinically significant risk of bleeding or fistula.5Study participants had a history of other malignancies within 3 years prior to the first administration of the study treatment intervention, or evidence of any residual lesions from previously diagnosed malignancies.6Participants in the study with active autoimmune diseases requiring systemic treatment within the past 2 years.7Previous systemic anti-tumor therapies include: a) Previous systemic treatment for locally advanced, unresectable, or metastatic NSCLC. b) Previous immunotherapy, excluding anti-PD-(L)1 (new) adjuvant therapy c) Previous use of ADCs containing MMAE payloads for treatment d) Previous pulmonary radiotherapy within 6 months prior to the first administration of the study treatment intervention, e) Previous systemic anti-angiogenic therapy (including but not limited to bevacizumab and its biosimilars, endotheliolin, small molecule TKIs, and rampoxilumab)
  • Exclusion Criteria:
  • *Participants with known AGAs including EGFR, ALK and ROS1, NTRK, BRAF, and MET
  • *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
  • *Known active CNS lesions, including brainstem, meningeal, or spinal cord metastases or compression
  • *Leptomeningeal disease
  • *Active autoimmune diseases requiring systemic treatment within the past 2 years
  • *Previous systemic anti-tumor therapy for locally advanced, unresectable, or metastatic NSCLC
  • *Previous treatment with immunotherapy (exception is (neo)adjuvant anti-PD-(L)1), ADCs containing MMAE payload, systemic anti-angiogenic therapy, or prior radiotherapy to the lung within 6 months of first dose of study intervention

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Los Angeles
Los Angeles, CA, United States, 90025
Investigator
Navid Hafez
Status
Will Be Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer