NCT02729298

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

Completed Phase 1 Last updated 14 November 2023

What this trial tests

Phase 1 trial testing TP-0903 in Advanced Solid Tumors in 177 participants. Completed in 29 June 2022.

Timeline

14 December 2016

Primary endpoint
29 June 2022

29 June 2022

Quick facts

Lead sponsor	Sumitomo Pharma America, Inc.
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	177
Start date	14 December 2016
Primary completion	29 June 2022
Estimated completion	29 June 2022
Sites	16 locations across United States

Drugs / interventions tested

• TP-0903 — full drug profile →

Conditions studied

• Advanced Solid Tumors — all drugs for Advanced Solid Tumors →
• EGFR Positive Non-small Cell Lung Cancer — all drugs for EGFR Positive Non-small Cell Lung Cancer →
• Colorectal Carcinoma — all drugs for Colorectal Carcinoma →
• Recurrent Ovarian Carcinoma — all drugs for Recurrent Ovarian Carcinoma →

Sponsor

Sumitomo Pharma America, Inc. — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors or EGFR Positive Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications.
   Zhu C, Wei Y, Wei X. · · 2019 · cited 398× · PMID 31684958 · DOI 10.1186/s12943-019-1090-3
2. Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment.
   Myers KV, Amend SR, Pienta KJ. · · 2019 · cited 333× · PMID 31088471 · DOI 10.1186/s12943-019-1022-2
3. Drugging the efferocytosis process: concepts and opportunities.
   Mehrotra P, Ravichandran KS. · · 2022 · cited 319× · PMID 35650427 · DOI 10.1038/s41573-022-00470-y
4. EGFR-TKIs resistance via EGFR-independent signaling pathways.
   Liu Q, Yu S, Zhao W, Qin S, et al · · 2018 · cited 283× · PMID 29455669 · DOI 10.1186/s12943-018-0793-1
5. Giving AXL the axe: targeting AXL in human malignancy.
   Gay CM, Balaji K, Byers LA. · · 2017 · cited 259× · PMID 28072762 · DOI 10.1038/bjc.2016.428
6. Emerging therapeutic agents for advanced non-small cell lung cancer.
   Chen R, Manochakian R, James L, Azzouqa AG, et al · · 2020 · cited 244× · PMID 32448366 · DOI 10.1186/s13045-020-00881-7
7. Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.
   Bhat GR, Sethi I, Sadida HQ, Rah B, et al · · 2024 · cited 170× · PMID 38329598 · DOI 10.1007/s10555-024-10172-z
8. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.
   Carter JL, Hege K, Yang J, Kalpage HA, et al · · 2020 · cited 148× · PMID 33335095 · DOI 10.1038/s41392-020-00361-x