First-in-human Study of Oral TP-0903 (a Novel Inhibitor of AXL Kinase) in Patients With Advanced Solid Tumors

Completed · Phase 1

Conditions studied: Advanced Solid Tumors, EGFR Positive Non-small Cell Lung Cancer, Colorectal Carcinoma, Recurrent Ovarian Carcinoma, BRAF-Mutated Melanoma

In brief

TP-0903 is a novel oral inhibitor that targets AXL kinase and reverses the mesenchymal phenotype associated with advanced cancers. Preclinical studies have shown promising antitumor activity of TP-0903 as a single agent against a variety of tumor types in both in vitro and in vivo studies. This first-in-human Phase 1a study is conducted to identify the maximum tolerated dose (MTD) of TP-0903 administered orally to patients with advanced solid tumors and to identify the safety profile and Recommended Phase 2 Dose (RP2D) of TP-0903. Once the MTD has been established, additional patients with specific tumor types (advanced solid tumors that have progressed after achieving a best documented response of at least stable disease (ie, SD, PR, or CR documented per iRECIST following at least 2 cycles (8 weeks) of immunotherapy, EGFR+ Non Small Cell Lung Cancer \[NSCLC\] and have demonstrated recent progression following a best documented response of at least stable disease (ie, SD, PR, or CR documented per RECIST v1.1 on ≤2 lines of oral TKIs (Prior chemotherapy ± immunotherapy is allowed as long as the patient is clearly demonstrating current progression on an EGFR TKI.), BRAF-, KRAS-, or NRAS-mutated Colorectal Carcinoma \[CRC\] for whom there is no standard therapy remaining, persistent/recurrent Ovarian Cancer who would be platinum refractory/ resistant and have had any number of lines of prior therapy, and BRAF-mutated Melanoma that has not responded to immunotherapy or a combination BRAF/MEK inhibitor) will be enrolled at the MTD in the Phase 1b study. Data collected from patients enrolled in each of these additional cohorts will be used for to confirm safety, explore potential biomarkers, and evaluate potential signals of activity when TP-0903 is administered to specific groups of heavily pretreated patients or given in combination with immunotherapy or a tyrosine kinase inhibitor (TKI). The study will investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity profiles.

Key facts

Study ID: NCT02729298
Run by: Sumitomo Pharma America, Inc.
People needed: 177
Starts: 2016-12-14
Expected to finish: 2022-06-29
Last updated by the study team: 2023-11-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

To be eligible for participation in the study, patients must meet all of the following inclusion criteria:
Patients enrolled in the Phase 1a study must:
Have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor
Be refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition
Patients enrolled in the Phase 1b study must meet criteria for one of the following tumor types:
Have tumors that have progressed after achieving a best documented response of at least stable disease (ie, SD, PR, or CR documented per iRECIST following at least 2 cycles (8 weeks) of immunotherapy and are felt to be appropriate for this type of treatment*
Have EGFR+ NSCLC and have demonstrated recent progression following a best documented response of at least stable disease (ie, SD, PR, or CR documented per per RECIST v1.1 on ≤2 lines of oral TKIs and are felt to be appropriate for this type of treatment* Prior chemotherapy ± immunotherapy is allowed as long as the patient is clearly demonstrating current progression on an EGFR TKI.
Have BRAF-, KRAS-, or NRAS-mutated CRC for whom there is no standard therapy remaining
Have persistent/recurrent ovarian cancer who would be platinum refractory/ resistant and have had any number of lines of prior therapy
Have BRAF-mutated melanoma that has not responded to immunotherapy or a combination BRAF/MEK inhibitor
Have one or more tumors measurable or evaluable as outlined by modified RECIST v1.1 or iRECIST
Have an Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO]) performance of ≤1
Have a life expectancy ≥3 months
Be ≥18 years of age
Have a negative pregnancy test (if female of childbearing potential)
Have acceptable liver function:
Bilirubin ≤1.5x upper limit of normal (ULN)
Patients receiving immunotherapy should have a bilirubin level <3.0x ULN.
Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤2.5x upper limit of normal (ULN)
If liver metastases are present, then ≤5x ULN is allowed.
Patients receiving immunotherapy should have AST and ALT levels <5.0x ULN.
Have acceptable renal function:
a. Calculated creatinine clearance ≥30 mL/min
Have acceptable hematologic status:
Granulocyte ≥1500 cells/mm3

Where it is running

Mayo Clinic Arizona — Phoenix, Arizona, United States
HonorHealth Research Institute — Scottsdale, Arizona, United States
University of Colorado Denver — Denver, Colorado, United States
US Oncology - Rocky Mountain Cancer Centers, LLP (RMCC) — Denver, Colorado, United States
Mayo Clinic Florida — Jacksonville, Florida, United States
Miami Cancer Institute — Miami, Florida, United States
University of Kansas Cancer Center — Fairway, Kansas, United States
Mayo Clinic Rochester — Rochester, Minnesota, United States
US Oncology - Willamette Valley Cancer Institute and Research Center — Eugene, Oregon, United States
US Oncology - Texas Oncology Austin — Austin, Texas, United States
University of Texas Southwestern Medical Center — Dallas, Texas, United States
US Oncology - Texas Oncology - Fort Worth — Fort Worth, Texas, United States
University of Texas Science Center at San Antonio (UTHSCSA) — San Antonio, Texas, United States
US Oncology - Texas Oncology - Tyler — Tyler, Texas, United States
US Oncology - Virginia Cancer Specialists (VCS) — Fairfax, Virginia, United States
Medical College of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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