PF-06939999 / Pfizer - LARVOL DELTA

A phase I study to evaluate the safety, pharmacokinetics, and pharmacodynamics of PF-06939999 (PRMT5 inhibitor) in patients with selected advanced or metastatic tumors with high incidence of splicing factor gene mutations. (PubMed, ESMO Open) - P1 | "PF-06939999 demonstrated a tolerable safety profile and objective clinical responses in a subset of patients, suggesting that PRMT5 is an interesting cancer target with clinical validation. However, no predictive biomarker was identified. The role of PRMT5 in cancer biology is complex and requires further preclinical, mechanistic investigation to identify predictive biomarkers for patient selection."

Journal • Metastases • P1 data • PK/PD data • Fatigue • Head and Neck Cancer • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • PRMT5

"Select projects targeting synthetic lethality TNG908 MRTX1719 SKL27969 AMG 193 AG-270 IDE397 JNJ-64619178 PRT543 PRT811 RP-6306 GSK3326595 GSK3368715 PF-06939999 JBI-778 TNG462 ISM020 AGX323 AT101/ AT201 @JacobPlieth @evaluatepharma https://t.co/74gBPzNLcn https://t.co/5Um0uV9GAB" (@BRAINCURES)

Synthetic lethality

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=56 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; The study has been terminated based on a strategic evaluation within the current Pfizer oncology portfolio. This decision is not due to any safety concerns or requests from any regulatory authorities.

Trial termination • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed | N=43 ➔ 56

Enrollment change • Trial completion • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=43; Active, not recruiting; Sponsor: Pfizer; Recruiting ➔ Active, not recruiting; N=140 ➔ 43; Trial completion date: Sep 2023 ➔ Apr 2022

Clinical • Enrollment change • Enrollment closed • Trial completion date • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=140; Recruiting; Sponsor: Pfizer; Trial completion date: Feb 2026 ➔ Sep 2023; Trial primary completion date: Aug 2024 ➔ Apr 2022

Clinical • Trial completion date • Trial primary completion date • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

SAM Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance. (PubMed, Mol Cancer Ther) - "Drug sensitivity to PF-06939999 in NSCLC cells associates with cancer pathways including MYC, cell cycle and spliceosome, and with mutations in splicing factors such as RBM10. Translation of efficacy in mouse tumor xenograft models with splicing mutations provides rationale for therapeutic use of PF-06939999 in the treatment of splicing dysregulated NSCLC."

Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PRMT5 • RBM10

[VIRTUAL] PF‑06939999, a potent and selective PRMT5 inhibitor, in patients with advanced or metastatic solid tumors: A phase 1 dose escalation study. (ASCO 2021) - P1 | "PF-06939999 showed dose-dependent and manageable toxicities in this phase 1 dose escalation study . Objective tumor responses were observed in pts with HNSCC and NSCLC . Analysis of archival tissue for the presence of splicing factor mutations and other potential predictive biomarkers is ongoing ."

Clinical • P1 data • Anemia • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Fatigue • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • Urothelial Cancer • PRMT5

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=140; Recruiting; Sponsor: Pfizer; Trial completion date: Jan 2024 ➔ Apr 2026; Trial primary completion date: Jul 2022 ➔ Oct 2024

Clinical • Trial completion date • Trial primary completion date • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=140; Recruiting; Sponsor: Pfizer; Trial completion date: Jul 2024 ➔ Jan 2024; Trial primary completion date: Jan 2023 ➔ Jul 2022

Clinical • Trial completion date • Trial primary completion date • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

[VIRTUAL] SAM competitive PRMT5 inhibitor PF06939999 demonstrates antitumor activity in splicing dysregulated NSCLC with decreased liability of drug resistance (AACR 2021) - "Drug sensitivity associates with cancer pathways including MYC, cell cycle and splicing. Translation of efficacy in mouse tumor xenograft models with splicing mutations provides rationale for therapeutic use of PF-06939999 for treatment of splicing dysregulated NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PRMT5

[VIRTUAL] Design and synthesis of carbonucleoside inhibitors of PRMT5 for the treatment of cancer: A desymmetrization approach (ACS-Sp 2021) - "Furthermore, we will describe high-throughput experimentation efforts, characterization studies, and methodology development en route to the synthesis of novel tetrahydroisoquinolines via rhodium catalyzed C-H activation. We will conclude with the discovery and profile of our clinical candidate PF-06939999."

Oncology • PRMT5

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=140; Recruiting; Sponsor: Pfizer; Trial completion date: Nov 2023 ➔ Jul 2024; Trial primary completion date: May 2022 ➔ Jan 2023

Clinical • Trial completion date • Trial primary completion date • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=140; Recruiting; Sponsor: Pfizer; N=50 ➔ 140; Trial completion date: Jul 2022 ➔ Nov 2023

Clinical • Enrollment change • Trial completion date • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

PF06939999 (IASLC-LCTT 2020) - No abstract available