Oraxol (oral paclitaxel/encequidar) / Hanmi, Guangzhou Xiangxue Pharma, Hope Pharm - LARVOL DELTA

Tolerability Assessment of Orally Administered Paclitaxel With Encequidar in Dogs With Spontaneous Malignancy. (PubMed, Vet Comp Oncol) - "Conclusions of this study define oral paclitaxel MTD in cancer-bearing dogs at 90 mg/m2 when given with encequidar for 3 consecutive days weekly for 3 weeks. Future Phase 2 trials evaluating the therapeutic activity of oral paclitaxel at its MTD co-administered with encequidar in defined tumour histologies are warranted."

Journal • Acute Kidney Injury • Gastrointestinal Disorder • Hematological Disorders • Immunology • Nephrology • Neutropenia • Oncology • Oral Cancer • Renal Disease

Oral Paclitaxel + Encequidar vs IV Paclitaxel in Treatment of HER2 Negative Metastatic Breast Cancer (clinicaltrials.gov) - P3 | N=340 | Not yet recruiting | Sponsor: Health Hope Pharma

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Phase I clinical trial to assess safety and efficacy of Oraxol, a novel oral paclitaxel chemotherapy agent, in patients with previously treated metastatic breast cancer. (PubMed, MedComm (2020)) - "Oraxol significantly alters metabolism and correlates with response and survival. In conclusion, Oraxol exhibited promising antitumor efficacy and manageable safety profiles in MBC patients."

Journal • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Co-release of paclitaxel and encequidar from amorphous solid dispersions increase oral paclitaxel bioavailability in rats. (PubMed, Int J Pharm) - "Interestingly, a noticeable increase in paclitaxel bioavailability of 24-fold was observed when paclitaxel and encequidar were co-administered as HPMC-5-based ASDs. We, therefore, suggest that controlling the release rate of paclitaxel and encequidar in order to obtain simultaneous and timed release from polymer-based ASDs is a strategy to increase oral paclitaxel bioavailability."

Journal • Preclinical

Genomic Landscape and Clinical Outcomes of Triple-Negative Invasive Lobular Carcinoma (SABCS 2023) - "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..."

Clinical • Clinical data • IO biomarker • Tumor mutational burden • Breast Cancer • Oncology • Triple Negative Breast Cancer • CDH1 • ER • PD-L1 • PIK3CA • TMB • TP53

Oral paclitaxel and encequidar in patients with breast cancer: a pharmacokinetic, safety, and antitumor activity study. (PubMed, Ther Adv Med Oncol) - P1 | "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."

Journal • PK/PD data • Breast Cancer • Febrile Neutropenia • Hematological Disorders • Neutropenia • Oncology • Pain • Solid Tumor

Oral paclitaxel, carboplatin, and dostarlimab (OPE/Cb/D) without and with trastuzumab in early-stage, high-risk breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL. (ASCO 2023) - P2 | "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."

Clinical • IO biomarker • Late-breaking abstract • Alopecia • Anemia • Breast Cancer • Endocrine Disorders • Febrile Neutropenia • Gastrointestinal Disorder • Hematological Disorders • HER2 Breast Cancer • Immune Modulation • Infectious Disease • Nephrology • Neutropenia • Oncology • Oral Cancer • Pain • Renal Disease • Solid Tumor • HER-2

Oral paclitaxel and dostarlimab with or without trastuzumab in early-stage, high-risk breast cancer: Results from the neoadjuvant ISPY 2 TRIAL. (ASCO 2023) - P2 | "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)."

Clinical • IO biomarker • Late-breaking abstract • Alopecia • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • Neutropenia • Oncology • Pain • Solid Tumor • HER-2

The Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol (clinicaltrials.gov) - P1 | N=29 | Terminated | Sponsor: Athenex, Inc. | Trial completion date: Oct 2023 ➔ May 2023 | Recruiting ➔ Terminated; STUDY HALTED DUE TO FINANCIAL CONTRAINTS

Trial completion date • Trial termination • Oncology • Solid Tumor

KEYNOTE-E06: Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=34 | Terminated | Sponsor: 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

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor

KX-ORAX-010t: A Study of Oraxol in Subjects With Cutaneous Angiosarcoma (clinicaltrials.gov) - P2 | N=48 | Completed | Sponsor: Athenex, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2023 ➔ May 2023 | Trial primary completion date: Sep 2023 ➔ May 2023

Trial completion • Trial completion date • Trial primary completion date • Angiosarcoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Solid Tumor

Hanmi Pharm's US partner for anticancer drug files for bankruptcy (Korea Biomedical Review) - "Athenex, the U.S. partner that aimed to commercialize Hanmi Pharm’s anticancer drug Oraxol, has recently initiated the asset-selling procedure subsequent to its filing for bankruptcy. According to industry watchers, Athenex recently filed for voluntary bankruptcy protection in the U.S. Bankruptcy Court in the Southern District of Texas. It has reached an agreement with its lenders to expedite the sale of the company's assets....As Athenex begins the process of selling its assets, industry watchers are closely watching if Athenex will also sell off rights to Oraxol."

Commercial • Angiosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

KEYNOTE-E06: Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=86 | Recruiting | Sponsor: Athenex, Inc. | Trial completion date: Jun 2023 ➔ Oct 2024 | Trial primary completion date: Mar 2023 ➔ Sep 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor

Quantum Leap Healthcare Collaborative Announces Result of Oral Paclitaxel in Combination with a PD-1 and Carboplatin from I-SPY2 TRIAL at ASCO (PRNewswire) - "Quantum Leap...and Athenex...will present the findings of the I-SPY 2 TRIAL evaluation of Athenex's oral paclitaxel plus encequidar in combination with GSK's dostarlimab in the neoadjuvant setting at this year's American Society of Clinical Oncology (ASCO) conference....Athenex...collaborated with GSK and Quantum Leap in two study arms of the I-SPY 2 TRIAL. The two arms included oral paclitaxel plus encequidar in combination with GSK's dostarlimab, an investigational antibody binding PD-1, with and without carboplatin followed by adriamycine and Cytoxan."

P2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Athenex Provides Fourth Quarter and Full Year 2022 Financial Results and Business Update (GlobeNewswire) - "Anticipated Upcoming Milestones: Plan to discuss the I-SPY 2 Phase 2 trial data with the FDA in connection with the New Drug Application (NDA) of Oral Paclitaxel for metastatic breast cancer;Data update from I-SPY 2 Phase 2 trial for Oral Paclitaxel regimen in the neoadjuvant breast cancer treatment setting anticipated at upcoming national meetings in 2Q 2023 by Quantum Leap Healthcare Collaborative; Expecting independent panel review of MHRA decision."

P2 data • Breast Cancer • Oncology

Effective preclinical management of angiosarcoma with oral paclitaxel (AACR 2019) - P1; "Oral paclitaxel (“Oraxol”; paclitaxel co-administered with HM30181A, a non-absorbable P-gp inhibitor) eliminates the risk of hypersensitivity to IV formulations while reducing neuropathy with the potential for improved efficacy. Cavernous blood-filled neoplastic vessels were consistently formed in vehicle and 10 mg/kg paclitaxel-treated groups. However, few to none were present in 20, 30, or 40 mg/kg paclitaxel-treated groups, suggesting oral paclitaxel demonstrated dose-dependent efficacy in this angiosarcoma murine model.Oral paclitaxel has been granted Orphan Drug Designation by the US FDA for the treatment of angiosarcomas and a pilot study of oral paclitaxel in patients with cutaneous angiosarcoma is planned (NCT03544567)."

Preclinical

KX-ORAX-010t: A Study of Oraxol in Subjects With Cutaneous Angiosarcoma (clinicaltrials.gov) - P2 | N=43 | Active, not recruiting | Sponsor: Athenex, Inc. | Trial completion date: Sep 2022 ➔ Sep 2023 | Trial primary completion date: Sep 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Angiosarcoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Solid Tumor

Athenex Announces MHRA Decision on Oral Paclitaxel (GlobeNewswire) - "Athenex, Inc....announced that its proprietary Oral Paclitaxel formulation did not receive regulatory approval from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) for metastatic breast cancer based solely on CMC issues. The MHRA application was not rejected based on any clinical efficacy or safety concerns expressed by the MHRA. MHRA regulations allow an applicant to request a re-examination of an opinion by an independent board which the Company plans to pursue."

European regulatory • Breast Cancer • Oncology

"Another option is oraxol if the clinical trial is available in the center." (@VivekSubbiah)

Clinical

Quantum Leap Healthcare Collaborative Announces Positive Result of Oral Paclitaxel in Combination with a PD-1 and Carboplatin from I-SPY2 TRIAL in Neoadjuvant Breast Cancer (PRNewswire) - "'It is important for us to seek out optimal combinations of therapies and find ways to reduce toxicity. We are excited to continue working on this and other combinations,' said Laura Esserman, MD, the lead investigator for the I-SPY 2 study and founder of QLHC."

Media quote

[VIRTUAL] Phase I study with expansion cohorts to assess the safety, tolerability, and activity of oral paclitaxel (oPac) + encequidar (E) in combination with pembrolizumab (Pem) in subjects with advanced solid malignancies (ESMO 2021) - P1 | "The addition of oPac/E to Pem was safe and the study successfully identified the RP2D. Encouraging anti-tumor activity was observed and phase 2 studies evaluating the combination are being planned."

Clinical • Combination therapy • P1 data • Bladder Cancer • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Urothelial Cancer • Uveal Melanoma

Assessing the Clinical Utility of Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer. (PubMed, J Clin Oncol) - No abstract available

Journal • Breast Cancer • Oncology • Solid Tumor

Oraxol + Encequidar (OPac+E) vs IV paclitaxel (IVPac) in the treatment of patients with metastatic breast cancer (mBC) (Study KX-ORAX-001): Subgroup survival analysis of patients with hepatic dysfunction (SABCS 2021) - "Although patients with mBC and mild hepatic dysfunction at baseline are at increased risk of early serious neutropenic and infectious/septic complications after treatment with oPAC+E, this risk is counterbalanced by an increase in overall survival. (NCT 02594371)"

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-1 • PGR

A novel oral paclitaxel and HM10381 (oraxel)-treated metastatic breast cancer: A phase I study (KX‑ORAX‑CN-007). (ASCO 2022) - P1 | "The study showed that Oraxol as novel oral chemotherapy agent shows promising antitumor activity in patients with metastatic breast cancer, manageable toxicity, and no hypersensitivity-type reactions."

P1 data • Breast Cancer • Febrile Neutropenia • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Solid Tumor

The Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Athenex, Inc. | Trial completion date: Oct 2022 ➔ Oct 2023 | Trial primary completion date: Jul 2022 ➔ Jul 2023

Trial completion date • Trial primary completion date • Oncology • Solid Tumor