EAY191-E4 (A ComboMATCH Treatment Trial) – Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients with Prior Taxane Treatment

The study chair for this treatment trial is Alice Chen, MD (National Cancer Institute).

Taxane therapies are part of the standard-of-care algorithm for multiple types of solid tumors in the advanced disease setting. However, as a monotherapy in advanced disease, particularly in patients whose cancer has progressed on prior taxane therapy, response rates are less than 10%.

Nilotinib is a BCR-ABL tyrosine kinase inhibitor (TKI) that is FDA-approved to treat adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP). The TKI is also FDA-approved to treat adult patients with CP and accelerated phase (AP) Ph+ CML who are resistant to or intolerant of therapy with imatinib. The major molecular response rate is around 60%. Currently, there is no known activity, or approval, for nilotinib in solid tumors.

Recent preclinical and early clinical research suggests that the combination of nilotinib plus the taxane drug paclitaxel (TAXOL®) may yield promising anticancer activity. The combination is being investigated by researchers at the National Cancer Institute (NCI) Developmental Therapeutics Clinic. In an ongoing phase 1 clinical trial (NCT02379416), the combination treatment demonstrated efficacy in patients with solid tumors, including partial responses in patients who did not benefit from prior taxane-based therapy. Further, the trial indicates that the nilotinib-paclitaxel combination may offer improved tolerability compared to paclitaxel monotherapy.

Through the phase 2 treatment trial EAY191-E4, part of the ComboMATCH precision medicine initiative, researchers will continue to evaluate the activity of nilotinib-paclitaxel in patients with solid tumors and explore predictive biomarkers of response and resistance. The study’s primary objective is to assess the proportion of patients with taxane-refractory advanced malignancies who have objective responses to treatment.

To take part in this treatment trial, patients must first enroll in the ComboMATCH registration trial (EAY191) to help determine eligibility. For EAY191-E4, patients must be adults with solid cancers and progressive disease who have been treated previously with taxane therapies. Approximately 40 people will participate in EAY191-E4.

Learn more about EAY191-E4 at ecog-acrin.org.

EAY191-E4 is part of ComboMATCH, a large precision medicine initiative with a coordinated set of clinical trials evaluating novel drug combinations. The ComboMATCH patient registration trial is being led by the ECOG-ACRIN Cancer Research Group and National Cancer Institute; treatment trials are being led by the Alliance for Clinical Trials in Oncology, Children’s Oncology Group, ECOG-ACRIN, NRG Oncology, and SWOG Cancer Research Network.