Phase 1 of PF-08046033 for advanced non-small-cell lung cancer, esophageal squamous cell cancer, and cutaneous melanoma

A Phase 1 Study to Investigate PF-08046033 in Participants With Advanced Solid Tumors

Phase 1 Interventional Pfizer · NCT07519655

This Phase 1 study will try the experimental antibody-drug conjugate PF-08046033 in adults whose non-small-cell lung cancer, esophageal squamous cell cancer, or cutaneous melanoma has progressed after standard treatments.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment250 (estimated)
Ages18 Years and up
SexAll
SponsorPfizer Industry-sponsored
Locations6 sites (Denver, Colorado and 5 other locations)
Trial IDNCT07519655 on ClinicalTrials.gov

What this trial studies

PF-08046033 is an antibody-drug conjugate being tested in adults with metastatic or unresectable non-small-cell lung cancer, esophageal squamous cell cancer, or cutaneous melanoma. The study begins with a dose-escalation phase to find a safe and tolerable dose and then opens expansion cohorts by tumor type to further define safety and early signs of anti-tumor activity. Key endpoints include safety, tolerability, pharmacokinetics, and preliminary tumor response. Eligible participants must have measurable disease and an ECOG performance status of 0–1.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed metastatic or unresectable non-small-cell lung cancer, esophageal squamous cell cancer, or cutaneous melanoma that has progressed after standard treatments, with measurable disease and ECOG 0–1.

Not a fit: Patients with active central nervous system metastases, significant pre-existing neuropathy (≥Grade 2), uncontrolled diabetes, prior GPNMB-targeted therapy, or known hypersensitivity to the drug formulation are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, PF-08046033 could offer a new treatment option that shrinks tumors or slows disease progression for patients who have exhausted standard therapies.

How similar studies have performed: Other antibody-drug conjugates have demonstrated anti-tumor activity in some cancers, but GPNMB-targeted therapies to date have shown mixed results and are still being evaluated.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Participants must have histologically-confirmed metastatic or unresectable locally advanced NSCLC, ESCC, or cutaneous melanoma.
2. Participants must have disease that has progressed on or be unable to tolerate standard treatments (Part 1) or 1-2 prior systemic therapies (Part 2).
3. Participants must have measurable disease.
4. Eastern Cooperative Oncology Group (ECOG) performance status is 0-1.

Exclusion Criteria:

1. Participants with known clinically active central nervous system (CNS) metastases.
2. Participants with pre-existing neuropathy ≥Grade 2 per NCI CTCAE v 5.0.
3. Uncontrolled diabetes mellitus with hemoglobin (Hgb) A1C ≥10.0%.
4. Untreated clinically significant thromboembolic disease.
5. Previous exposure to GPNMB-targeted therapy.
6. Known or suspected hypersensitivity to any component or excipient contained in the drug formulation of study intervention.

Where this trial is running

Denver, Colorado and 5 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Non-Small-Cell LungEsophageal CancerCutaneous MelanomaLung cancerEsophageal cancerMelanomaAntibody drug conjugate
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.