PF-08046032 / Pfizer - LARVOL DELTA

OX40-ADC, a potential new class of cancer immunotherapy by depleting Treg within TME (SITC 2025) - "One attempt by CD25-ADC (ADCT-301) failed for severe toxicities. A new CD25-ADC (PF-08046032) with attenuated affinity to CD25 and a less toxic VC-MMAE demonstrated preferential killings of TIL-Treg over peripheral Treg or CD8+ T cells, expecting widened therapeutic window...We plan to present the preliminary data of these studies during the meeting.Conclusions OX40-ADC can potentially deplete TIL-Treg to enhance tumor immunity/anti-tumor activities in animal models. HX111 could be such a candidate drug for tumor treatment, with enhanced efficacy when combined with PD-1 blockades."

Oncology • CCR8 • CD4 • CD8 • IL2RA

A Study to Learn About the Study Medicine Called PF-08046031 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=185 ➔ 11 | Trial completion date: Jun 2030 ➔ Feb 2026 | Trial primary completion date: Jun 2029 ➔ Feb 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=220 ➔ 6 | Trial completion date: Apr 2029 ➔ Feb 2026 | Trial primary completion date: Jan 2029 ➔ Feb 2026

Enrollment change • Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • B Cell Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • T Cell Non-Hodgkin Lymphoma

A Clinical Trial of PF-08046037 Alone or With Sasanlimab in Patients With Advanced or Metastatic Malignancies (clinicaltrials.gov) - P1 | N=399 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2029 ➔ Jul 2029 | Trial primary completion date: Feb 2028 ➔ Jul 2028

Enrollment open • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study to Learn About the Study Medicine Called PF-08046031 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=185 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor

A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers. (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • B Cell Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • T Cell Non-Hodgkin Lymphoma

A Clinical Trial of PF-08046037 Alone or With Sasanlimab in Patients With Advanced or Metastatic Malignancies (clinicaltrials.gov) - P1 | N=399 | Not yet recruiting | Sponsor: Pfizer

Monotherapy • New P1 trial • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PF-08046032: A novel, investigational CD25-directed antibody-drug conjugate optimized for selective depletion of regulatory T cells in advanced malignant tumors. (PubMed, Mol Cancer Ther) - "Lastly, PF-08046032 was well-tolerated in non-human primates and mitigated the persistent depletion of peripheral blood Treg that was observed with a high affinity anti-CD25 ADC comparator, demonstrating the safety benefit of a detuned affinity ADC format. PF-08046032 represents an innovative therapeutic approach for depletion of intratumoral Tregs that may offer an improved safety profile and efficacy over traditional Treg depleting agents."

IO biomarker • Journal • Hematological Malignancies • Immunology • Lymphoma • Oncology • Solid Tumor • CD8 • IL2 • IL2RA

PF-08046032: a CD25-directed vedotin ADC leveraging a well characterized safety and pharmacokinetic profile for enhanced regulatory T cell depletion in the tumor microenvironment (AACR 2025) - "Leveraging the cumulative knowledge of the vedotin platform, PF-08046032 enables a novel additional mechanism of action for vedotin ADCs at potentially efficacious and safe doses. These data support further investigation of PF-08046032 in clinical trials for advanced malignancies."

Biomarker • Clinical • IO biomarker • PK/PD data • Tumor microenvironment • Colorectal Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • CD8 • IL2 • IL2RA • ISG20

This is a Study to Learn About How the Combination of the Study Medicines Sigvotatug Vedotin Plus Pembrolizumab Works in People With Non-small Cell Lung Cancer With High Levels of PD-L1. (clinicaltrials.gov) - P3 | N=714 | Not yet recruiting | Sponsor: Pfizer | Initiation date: Jan 2025 ➔ May 2025

Monotherapy • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers. (clinicaltrials.gov) - P1 | N=220 | Not yet recruiting | Sponsor: Pfizer

Monotherapy • New P1 trial • B Cell Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • T Cell Non-Hodgkin Lymphoma