PF-07209960 / Pfizer - LARVOL DELTA

First-in-human phase I study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of PF-07209960 in patients with advanced or metastatic solid tumors. (PubMed, ESMO Open) - P1 | "PF-07209960 was generally manageable, with potential antitumor activity in some patients."

Journal • P1 data • PK/PD data • Colorectal Cancer • Hematological Disorders • Oncology • Solid Tumor • IL15

Pharmacokinetics, pharmacodynamics, and toxicity of a PD-1-targeted IL-15 in cynomolgus monkeys. (ASCO 2024) - "PF-07209960 demonstrated dose-dependent exposure and robust PD (T cell and NK cell subsets expansion and cytokine release) in cynomolgus monkeys, with well-characterized safety profile. In summary, the results of the present study support Phase I clinical evaluation of PF-07209960 in cancer patients."

PK/PD data • Hematological Disorders • Oncology • Thrombocytopenia • CD4 • CD8 • IL10 • IL15 • IL6 • STAT5

Preclinical characterization of MBS309, a conditionally active PD-1-dependent IL-2 mutation with significantly superior anti-tumor efficacy with safety (AACR 2024) - "In our in vivo tumor murine models, 1mg/kg MBS309 showed much better suppression effect in MC38/hPD-L1 tumor than 1mg/kg RG6279 analog and Pembrolizumab (1mg/kg) combination with wild type IL-2 (0.1mg/kg); And MBS309 at the dosage of 5mg/kg can significantly inhibit tumor growth in PD-1 resistant Pan-02 xenograft models without any side-effects observed, while RG6279 analog at the dosage of 5mg/kg induced severe body reduction of the mice and resulted in 80% (4/5) mice death after two dosages...20mg/kg of MBS309 was well tolerated in mouse, while 10mg/kg of RG6279 analog or PF-07209960 analog show severe toxicity and resulted in death of all the mice...And it shows much higher anti-tumor effect compared to anti-PD-1/-L1 antibodies alone in both PD-1 sensitive and resistant tumor models. MBS309 has demonstrated a favorable safety profile and highly anti-tumor activities in vivo, which has the potential to supporting its clinical development for the treatment of cancer."

IO biomarker • Preclinical • Oncology • CD8 • IL2 • PD-1

Pharmacokinetics, pharmacodynamics, and toxicity of a PD-1-targeted IL-15 in cynomolgus monkeys. (PubMed, PLoS One) - "PF-07209960 is a novel bispecific fusion protein composed of an anti-PD-1 antibody and engineered IL-15 cytokine mutein with reduced binding affinity to its receptors...At scheduled necropsy, microscopic findings were generalized mononuclear infiltration in various tissues. Both the no observed adverse effect level (NOAEL) and the highest non severely toxic dose (HNSTD) were determined to be 0.3 mg/kg/dose, which corresponded to mean Cmax and AUC48 values of 1.15 μg/mL and 37.9 μg*h/mL, respectively."

Journal • PK/PD data • CD4 • CD8 • IFNG • IL10 • IL15 • IL6 • STAT5

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=36 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; Pfizer has made an internal business decision to not continue further development of PF-07209960. This decision was not based on safety or regulatory considerations

Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed | Trial completion date: Feb 2024 ➔ May 2023 | Trial primary completion date: Feb 2024 ➔ May 2023

Metastases • Trial completion • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=37 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Jul 2025 ➔ Feb 2024

Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=172 ➔ 31 | Trial completion date: Mar 2025 ➔ Jul 2025 | Trial primary completion date: Oct 2023 ➔ Feb 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=172; Recruiting; Sponsor: Pfizer; Trial completion date: Aug 2025 ➔ Mar 2025

Clinical • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=172; Recruiting; Sponsor: Pfizer; Trial completion date: Sep 2023 ➔ Aug 2025

Clinical • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=172; Recruiting; Sponsor: Pfizer; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=172; Not yet recruiting; Sponsor: Pfizer

Clinical • New P1 trial • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer