Related Experiment Video
Updated: Jul 29, 2026
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with
Timothy A Yap1, Maria Vieito2, Capucine Baldini3
1Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas. tyap@mdanderson.org.
Purpose:
A novel, selective, next-generation transforming growth factor beta (TGFβ) receptor type-1 small molecule inhibitor, LY3200882, demonstrated promising preclinical data. This first-in-human trial evaluated safety, tolerability, recommended phase II dose (RP2D), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882 as monotherapy or with other anticancer agents in patients with advanced cancer.
Patients And Methods:
This phase I multicenter study of oral LY3200882 (NCT02937272) comprised dose escalation, monotherapy expansion in grade 4 glioma, and combination therapy in solid tumors (LY3200882 and PD-L1 inhibitor LY3300054), pancreatic cancer (LY3200882, gemcitabine, and nab-paclitaxel), and head and neck squamous cell cancer (LY3200882, cisplatin, and radiation).
Results:
Overall, 139 patients with advanced cancer were treated. The majority (93.5%) of patients experienced ≥1 treatment-emergent adverse events (TEAE), with 39.6% LY3200882-related. Grade 3 LY3200882-related toxicities were only observed in combination therapy arms. One patient in the pancreatic cancer arm experienced cardiovascular toxicity. The LY3200882 monotherapy RP2Ds were established in two schedules: 50 mg twice a day 2-weeks-on/2-weeks-off and 35 mg twice a day 3-weeks-on/1-week-off. Four patients with grade 4 glioma had durable Revised Assessment in Neuro Oncology (RANO) partial responses (PR) with LY3200882 monotherapy (n = 3) or LY3200882-LY3300054 combination therapy (n = 1). In treatment-naïve patients with advanced pancreatic cancer, 6 of 12 patients achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 PR and 3 of 12 patients demonstrated stable disease, for an overall 75% disease-control rate with the combination of LY3200882, gemcitabine, and nab-paclitaxel.
Conclusions:
LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in pancreatic cancer. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced pancreatic cancer are warranted.
Insights
The novel TGFβ inhibitor LY3200882 showed promising safety and antitumor activity in advanced cancers. Pancreatic cancer patients demonstrated significant disease control with LY3200882 combination therapy.
Area of Science:
- Oncology
- Translational Medicine
- Pharmacology
Background:
- Transforming growth factor beta (TGFβ) signaling is implicated in cancer progression.
- LY3200882 is a novel, selective, next-generation TGFβ receptor type-1 small molecule inhibitor with promising preclinical data.
Purpose of the Study:
- To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882.
- To determine the recommended phase II dose (RP2D) of LY3200882.
- To assess LY3200882 as monotherapy and in combination with other anticancer agents in patients with advanced cancer.
Main Methods:
- A phase I multicenter study (NCT02937272) involving dose escalation and expansion cohorts.
- Patients received oral LY3200882 as monotherapy (grade 4 glioma) or in combination therapies (solid tumors, pancreatic cancer, head and neck squamous cell cancer).
- Combination regimens included LY3200882 with PD-L1 inhibitor LY3300054, or with gemcitabine and nab-paclitaxel, or with cisplatin and radiation.
Main Results:
- 139 patients with advanced cancer were treated. Most experienced treatment-emergent adverse events (TEAEs), with 39.6% related to LY3200882. Grade 3 toxicities were limited to combination arms.
- RP2Ds for LY3200882 monotherapy were established: 50 mg BID (2-weeks-on/2-weeks-off) and 35 mg BID (3-weeks-on/1-week-off).
- Durable partial responses (PR) were observed in 4 patients with grade 4 glioma. In treatment-naïve advanced pancreatic cancer, the combination of LY3200882, gemcitabine, and nab-paclitaxel achieved a 75% disease-control rate (6 PR, 3 stable disease).
Conclusions:
- LY3200882, as monotherapy and in combination, was safe and well-tolerated.
- Preliminary antitumor activity was observed, particularly in advanced pancreatic cancer.
- Further studies evaluating LY3200882 in combination with gemcitabine and nab-paclitaxel for advanced pancreatic cancer are warranted.
More Related Videos
11:06Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
