NCT02546531

Defactinib Combined With Pembrolizumab and Gemcitabine in Patients With Advanced Cancer

Completed Phase 1 Last updated 20 July 2021

What this trial tests

Phase 1 trial testing Defactinib in Advanced Solid Tumors in 43 participants. Completed in 11 January 2021.

Timeline

3 February 2016

Primary endpoint
17 November 2017

11 January 2021

Quick facts

Lead sponsor	Washington University School of Medicine
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	43
Start date	3 February 2016
Primary completion	17 November 2017
Estimated completion	11 January 2021
Sites	2 locations across United States

Drugs / interventions tested

• Defactinib — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →

Conditions studied

• Advanced Solid Tumors — all drugs for Advanced Solid Tumors →
• Solid Tumors — all drugs for Solid Tumors →
• Pancreatic Cancer — all drugs for Pancreatic Cancer →

Sponsor

Washington University School of Medicine

Who can join

18 and older, any sex, with Advanced Solid Tumors or Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

In pancreatic cancer, targeting the tumor microenvironment has become a promising therapeutic strategy. Focal adhesion kinase (FAK) pathway activation is essential for promoting a fibrotic and inflammatory tumor microenvironment, and FAK inhibitors have demonstrated reasonable anti-tumor activity in the preclinical setting. Furthermore, a maximal synergetic effect was achieved when a FAK inhibitor was given in combination with a PD-1 antagonist and chemotherapy in multiple pancreas tumor animal models. This supports the concept of using FAK inhibitors to reduce stromal fibrosis during checkpoint immunotherapeutic treatment. Therefore, these robust preclinical findings will be tested in the proposed phase I trial.

Publications & conference data

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

1. Every step of the way: integrins in cancer progression and metastasis.
   Hamidi H, Ivaska J. · · 2018 · cited 1134× · PMID 30002479 · DOI 10.1038/s41568-018-0038-z
2. The tumour microenvironment in pancreatic cancer - clinical challenges and opportunities.
   Ho WJ, Jaffee EM, Zheng L. · · 2020 · cited 963× · PMID 32398706 · DOI 10.1038/s41571-020-0363-5
3. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy.
   Jiang H, Hegde S, Knolhoff BL, Zhu Y, et al · · 2016 · cited 829× · PMID 27376576 · DOI 10.1038/nm.4123
4. Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies.
   Anderson KG, Stromnes IM, Greenberg PD. · · 2017 · cited 570× · PMID 28292435 · DOI 10.1016/j.ccell.2017.02.008
5. Challenges and Opportunities for Pancreatic Cancer Immunotherapy.
   Bear AS, Vonderheide RH, O'Hara MH. · · 2020 · cited 500× · PMID 32946773 · DOI 10.1016/j.ccell.2020.08.004
6. Fibrosis and cancer: A strained relationship.
   Piersma B, Hayward MK, Weaver VM. · · 2020 · cited 500× · PMID 32147542 · DOI 10.1016/j.bbcan.2020.188356
7. The Extracellular Matrix Modulates the Metastatic Journey.
   Kai F, Drain AP, Weaver VM. · · 2019 · cited 429× · PMID 31063753 · DOI 10.1016/j.devcel.2019.03.026
8. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies.
   Adamska A, Domenichini A, Falasca M. · · 2017 · cited 429× · PMID 28640192 · DOI 10.3390/ijms18071338