Oraxol (oral paclitaxel/encequidar)

She was diagnosed with TN ILC of the left supraclavicular nodes in 2022; she did not exhibit a response to docetaxel and carboplatin with pembrolizumab, and she subsequently received palliative radiation followed by capecitabine. Another patient with locally advanced TN ILC progressed on the KEYNOTE-522 regimen, immediately developed metastases, and is currently receiving palliative sacituzumab govitecan. The third patient with cT3N1 TN ILC progressed on neoadjuvant therapy (through the I-SPY 2 trial) with oral paclitaxel, encequidar, and dostarlimab, followed by dostarlimab with dose-dense doxorubicin and cyclophosphamide...She received comprehensive chest wall and nodal radiation and is currently receiving palliative capecitabine with neratinib given a high variant allele frequency driver somatic ERBB2 mutation... The most common somatic mutations among TN ILC patients included in this study were in CDH1, TP53, and PIK3CA. Currently the management of TN ILC is extrapolated from that of TN IDC, however our patients did not respond to chemoimmunotherapy. The presence of HER2-low status or somatic ERBB2 mutations may provide opportunities for treatment with an anti-HER2 antibody-drug conjugate or tyrosine kinase inhibitor.

There was a high rate of radiologically assessed clinical benefit, and a low rate of neurotoxicity which may provide advantages over IV paclitaxel. ClinicalTrials.gov Identifier: NCT03165955.

P1, N=29, Terminated, Athenex, Inc. | Trial completion date: Oct 2023 --> May 2023 | Recruiting --> Terminated; STUDY HALTED DUE TO FINANCIAL CONTRAINTS

P1, N=34, Terminated, Athenex, Inc. | N=86 --> 34 | Trial completion date: Oct 2024 --> May 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2024 --> May 2023; Study terminated due to lack of funding

P2, N=48, Completed, Athenex, Inc. | Active, not recruiting --> Completed | Trial completion date: Sep 2023 --> May 2023 | Trial primary completion date: Sep 2023 --> May 2023

P1, N=86, Recruiting, Athenex, Inc. | Trial completion date: Jun 2023 --> Oct 2024 | Trial primary completion date: Mar 2023 --> Sep 2024

Oral Paclitaxel and encequidar (OPE) is an oral combination of paclitaxel (P) with a p-glycoprotein pump inhibitor, encequidar...Treatment included OPE (Oral P 205mg/m2 + encequidar 12.9mg) on days 1-3 weekly x 12 and D 500 mg IV given q 3 weeks x 4, followed by doxorubicin/cyclophosphamide (AC) q 2-3 weeks x 4... Although both OPE and D have both been shown to have efficacy in other settings, combination therapy with OPE + D did not graduate in any of the predefined subtypes. In the HR+ signature where we would not expect a benefit of D, we see equal response to OPE with decreased rates of peripheral neuropathy and alopecia, which suggest this oral agent may be an attractive alternative to IV P in this subgroup and is under consideration in ISPY 2.2. We did not observe the expected improvement in pCR rates seen with PD-1 inhibitors in the HR- or MP2 subtypes (over P alone historic control).

Oral paclitaxel and encequidar (OPE) is an oral combination of paclitaxel (P) with a p-glycoprotein pump inhibitor, encequidar, to enhance gastrointestinal (GI) absorption...Treatment included Oral Paclitaxel 205mg/m2 and encequidar 12.9 mg on days 1-3, Carboplatin (Cb) AUC 1.5 on day 1 weekly x 12, and Dostarlimab (D) 500 mg every 3 weeks x 4, followed by doxorubicin/ cyclophosphamide (AC) every 2-3 weeks x 4... OPE/Cb/D graduated in the TN signature with a higher predicted pCR rate compared to control. OPE and D have been, individually, shown to have efficacy in other settings. The lower-than-expected pCR rate and lower irAEs with triplet therapy (taxane, platinum, immune checkpoint inhibitor [ICI]) in TN compared to prior IV chemo + ICI arms on I-SPY 2 suggests a possible interference of OPE with ICI.

P1b, N=36, Active, not recruiting, Athenex, Inc. | Trial completion date: Dec 2021 --> Dec 2022

P2; Trial completion date: Dec 2026 --> Dec 2031 | Trial primary completion date: Dec 2025 --> Dec 2030

P1b, N=36, Active, not recruiting, Athenex, Inc. | Trial completion date: Jul 2021 --> Dec 2021

P1b, N=36, Active, not recruiting, Athenex, Inc. | Trial completion date: Mar 2021 --> Jul 2021

P2, N=4000, Recruiting, QuantumLeap Healthcare Collaborative | Phase classification: P1 --> P2

P1, N=114, Recruiting, Athenex, Inc. | Trial completion date: Dec 2022 --> Jun 2023 | Trial primary completion date: Oct 2020 --> Mar 2023

P1, N=4000, Recruiting, QuantumLeap Healthcare Collaborative | Phase classification: P2 --> P1

P1b, N=36, Active, not recruiting, Athenex, Inc. | Recruiting --> Active, not recruiting | N=18 --> 36 | Trial completion date: Dec 2019 --> Mar 2021 | Trial primary completion date: Dec 2019 --> Dec 2020

P2, N=4000, Recruiting, QuantumLeap Healthcare Collaborative | N=1920 --> 4000

P2, N=1920, Recruiting, QuantumLeap Healthcare Collaborative | Trial primary completion date: Dec 2020 --> Dec 2025