tesetaxel (DJ 927) / Daiichi Sankyo, Odonate Therap - LARVOL DELTA

Systemic therapy for breast cancer brain metastases (SABCS 2019) - P2; "For patients with HER2-positive breast cancer, the combination of lapatinib and capecitabine has been associated with CNS response rates of 66% in the upfront setting, and 18-38% in patients whose disease has progressed after prior radiotherapy...The TBCRC 022 trial is now enrolling to a cohort who will receive ado-trastuzumab emtansine + neratinib...Notably, patients with brain metastases (either stable or progressive) are allowed on the current tucatinib registration trial (HER2CLIMB; NCT02614794). Finally, there is evidence that monoclonal antibodies and antibody drug conjugates may have CNS activity; for example, trastuzumab-emtansine has been reported to lead to CNS regressions in up to 40% of patients, based upon case series from several institutions, and in preliminary data from the PATRICIA study, the regimen of high dose trastuzumab (6 mg/kg weekly) plus pertuzumab was associated with CNS responses and prolonged stable disease in a subset of patients...Results..."

Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Tesetaxel, a novel, oral taxane, crosses intact blood-brain barrier (BBB) at therapeutically relevant concentrations (AACR 2019) - P3; "The taxanes paclitaxel (P) and docetaxel (D) do not significantly cross the BBB (brain to plasma exposure of only 1% and 8%, respectively), making them ineffective in treating CNS metastases. In dogs and monkeys, T brain concentrations far exceed its tumor GI50 for a sustained period when administered at therapeutically relevant concentrations. The inclusion criteria for the ongoing Phase 3 study of T in patients with aBC allows for CNS metastases."

"Still do not understand why the development of Tesetaxel was discontinued. Ideal space for big pharma to buy up the asset and bring it to the market !" (@RenoHemonc)

[VIRTUAL] Results from CONTESSA: A phase 3 study of tesetaxel plus a reduced dose of capecitabine versus capecitabine alone in patients with HER2-, hormone receptor + (HR+) metastatic breast cancer (MBC) who have previously received a taxane (SABCS 2020) - "An all-oral regimen of tesetaxel plus a reduced dose of capecitabine significantly improved PFS versus capecitabine alone. Neutropenia was the most frequent Grade ≥3 TEAE. Rates of clinically significant alopecia and neuropathy were low."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

More Innovation Is on Tap for 2021: Five Experts Describe Key Trends (OncLive) - "Novel therapeutic strategies that are likely to advance this year include expansion of uses for tyrosine kinase inhibitors, new combinations incorporating checkpoint immunotherapy, and progress in developing personalized cancer vaccines, according to Howard A. 'Skip' Burris III, MD....'2021 is going to be a refreshing year in many ways, with a lot of new data and advances for our patients with breast cancer,' said Tripathy...In targeted therapies, Tripathy expects the science to move forward on AKT inhibitors even though 1 agent in this class, ipatasertib, failed to show a significant improvement in PFS in combination with paclitaxel compared with placebo plus paclitaxel in patients with locally advanced, unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alterations in the IPATunity130 trial (NCT03337724)...Neeraj Agarwal, MD..."

Media quote • Renal Cell Carcinoma

CONTESSA: A multinational, multicenter, randomized, phase III registration study of tesetaxel plus a reduced dose of capecitabine in patients (pts) with HER2-, hormone receptor + (HR+) locally advanced or metastatic breast cancer (LA/MBC) who have previously received a taxane. (ASCO 2019) - P3; "Following review in Jan 2019, the Independent Data Monitoring Committee recommended that the Study continue as planned. Clinical trial information: NCT03326674"

Clinical • P3 data

Contessa: A multinational, multicenter, randomized, phase 3 registration study of tesetaxel in patients (Pts) with HER2-, hormone receptor + (HR+) locally advanced or metastatic breast cancer (MBC). (ASCO 2018) - P3; "555 pts have been treated with T in clinical studies (492 monotherapy; 63 in combination with capecitabine (C)). CONTESSA is 90% powered to detect a 42% improvement in PFS (HR = 0.71). Secondary endpoints are OS, ORR assessed by IRC, disease control rate assessed by IRC and patient reported outcomes."

Clinical • P3 data • HER2 Breast Cancer • Hormone Receptor Breast Cancer

[VIRTUAL] Results from CONTESSA 2: A multinational, multicenter, phase 2 study of tesetaxel (T) plus a reduced dose of capecitabine (C) in patients (pts) with hormone receptor + (HR+), HER2- metastatic breast cancer (MBC) not previously treated with a taxane. (ASCO 2021) - P2 | "An all-oral regimen of T plus a reduced dose of C demonstrated a high level of antitumor activity in pts with HR+, HER2- MBC not previously treated with a taxane . The confirmed ORR was 51%, median DoR was 9.5 mo and median PFS was 12.9 mo . Neutropenia was the most frequent Gr ≥3 TEAE; the rate of febrile neutropenia was 4.7% ."

Clinical • P2 data • Alopecia • Anemia • Breast Cancer • Dermatology • Hematological Disorders • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Immunology • Leukopenia • Neutropenia • Oncology • Pain • Solid Tumor • HER-2

[VIRTUAL] CONTESSA TRIO: A multinational, multicenter, phase (P) II study of tesetaxel (T) plus three different PD-(L)1 inhibitors in patients (Pts) with metastatic triple-negative breast cancer (TNBC) and tesetaxel monotherapy in elderly pts with HER2-metastatic breast cancer (MBC). (ASCO 2020) - P2 | "Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the treatment of multiple types of cancer; atezolizumab, in combination with nab-paclitaxel, was recently approved in the US for the treatment of metastatic TNBC. The study was initiated in March 2019. Research Funding: Odonate Therapeutics, Inc"

Clinical • Monotherapy • Breast Cancer • HER2 Breast Cancer • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Activity of tesetaxel, an oral taxane, given as a single-agent in patients (Pts) with HER2-, hormone receptor + (HR+) locally advanced or metastatic breast cancer (MBC) in a phase 2 study. (ASCO 2018) - P2; "T, as a single agent, was well tolerated with significant activity in pts with HER2-, HR+ MBC. T is currently being investigated in CONTESSA, a multinational, multicenter, randomized, Phase 3 study in pts with HER2-, HR+ MBC"

Clinical • P2 data • HER2 Breast Cancer • Hormone Receptor Breast Cancer

CONTESSA TRIO: A multinational, multicenter, phase 2 study of tesetaxel plus 3 different PD-(L)1 inhibitors in patients with metastatic triple-negative breast cancer (TNBC) and tesetaxel monotherapy in elderly patients with HER2- metastatic breast cancer (MBC) (SABCS 2019) - P2; "Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the treatment of multiple types of cancer; atezolizumab, in combination with nab-paclitaxel, was recently approved in the U.S. for the treatment of metastatic TNBC. The Study was initiated in March 2019. For further information on this trial, email joconnell@odonate.com or visit clinicaltrials.gov (NCT03952325)."

Clinical • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

CONTESSA 2: A multinational, multicenter, phase 2 study of tesetaxel plus a reduced dose of capecitabine in patients with HER2-, HR+ metastatic breast cancer (MBC) who have not previously received a taxane (SABCS 2019) - P2; "Enrollment was initiated in January 2019. For further information on this trial, email joconnell@odonate.com or visit clinicaltrials.gov (NCT03858972)."

Clinical • P2 data • HER2

CONTESSA: A multinational, multicenter, randomized, phase 3 registration study of testaxel plus a reduced dose of capecitabine in patients with HER2-, hormone receptor + (HR+) metastatic breast cancer (MBC) who have previously received a taxane (SABCS 2019) - P3; "Tesetaxel is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and once every 3 week (Q3W) dosing; no observed hypersensitivity reactions; preclinical evidence of central nervous system (CNS) penetration; and improved activity against chemotherapy-resistant tumors. The interim efficacy futility analysis was based on a pre-specified analysis of the first approximate 100 PFS events that occurred in the study. For further information on this trial, email joconnell@odonate.com or visit clinicaltrials.gov (NCT03326674)."

Clinical • P3 data • HER2

"Surprised that one of the big pharma did not buy out Tesetaxel rights and ran an appropriate study.." (@RenoHemonc)

The Effect of Tesetaxel on the QTc Interval and the Effect of Food, Itraconazole, and Rifampin on Tesetaxel Pharmacokinetics in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=93; Terminated; Sponsor: Odonate Therapeutics, Inc.; Active, not recruiting ➔ Terminated; The Sponsor has discontinued the development of tesetaxel

Clinical • Trial termination • Oncology • Solid Tumor

CONTESSA TRIO: Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC and Tesetaxel Monotherapy in Patients With HER2-Negative MBC (clinicaltrials.gov) - P2; N=294; Terminated; Sponsor: Odonate Therapeutics, Inc.; Trial completion date: Aug 2023 ➔ Jun 2021; Recruiting ➔ Terminated; Trial primary completion date: Aug 2022 ➔ Jun 2021; The Sponsor has discontinued the development of tesetaxel

Clinical • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PD-L1 • PGR

CONTESSA: Tesetaxel Plus Reduced Dose of Capecitabine vs. Capecitabine in HER2 Negative, HR Positive, LA/MBC (clinicaltrials.gov) - P3; N=685; Terminated; Sponsor: Odonate Therapeutics, Inc.; Trial completion date: Mar 2023 ➔ Jun 2021; Active, not recruiting ➔ Terminated; The Sponsor has discontinued the development of tesetaxel

Clinical • Trial completion date • Trial termination • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • MRI • PGR

CONTESSA 2: Tesetaxel Plus Reduced Dose of Capecitabine in Patients With HER2 Negative, HR Positive, LA/MBC (clinicaltrials.gov) - P2; N=152; Terminated; Sponsor: Odonate Therapeutics, Inc.; Trial completion date: Mar 2022 ➔ Jun 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Mar 2021 ➔ Jun 2021; The Sponsor has discontinued the development of tesetaxel

Clinical • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • MRI

"Hi, Dr. any thought using Tesetaxel will cause high Neutropenia?" (@sugarleon)

Hematological Disorders • Neutropenia

OneOncology Experts to Make 23 presentations at ASCO (PRNewswire) - "OneOncology...said...that partner practice physicians and other OneOncology experts will make 23 presentations across 12 different subject categories at the 2021 ASCO Annual Meeting from June 4-6...Category: Breast Cancer – Efficacy of enobosarm, a selective androgen receptor (AR) targeting agent, correlates with the degree of AR positivity in advanced AR+/estrogen receptor (ER)+ breast cancer in an international phase 2 clinical study; ABSTRACT: 1020 - Results from CONTESSA 2: A multinational, multicenter, phase 2 study of tesetaxel (T) plus a reduced dose of capecitabine (C) in patients (pts) with hormone receptor + (HR+), HER2- metastatic breast cancer (MBC) not previously treated with a taxane."

P1 data • P2 data • P3 data • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer

Odonate Therapeutics Announces Financial Results for the Three Months Ended March 31, 2021 (Businesswire) - "Odonate recently announced the discontinuation of development of tesetaxel and its intent to wind down tesetaxel-related operations. Odonate is working with clinical sites to transition patients in ongoing tesetaxel studies to appropriate alternative therapies or facilitate continuation of treatment with tesetaxel under compassionate use programs where appropriate....As of March 31, 2021, Odonate had $133.2 million in cash compared to $157.3 million as of December 31, 2020. "

Clinical • Commercial • Oncology

A Look Ahead to the 2020 SABCS Virtual Symposium (Clinical Care Options) - "For patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC), an update of the phase III KEYNOTE-355 study (GS3-01) will provide key information on PFS outcomes for each chemotherapy partner as well as additional efficacy endpoints for first-line pembrolizumab plus chemotherapy, a regimen that was approved by the FDA in November 2020 for patients with locally recurrent unresectable or metastatic TNBC and PD-L1 CPS ≥ 10 based on the significant PFS benefit shown in a prespecified interim analysis."

Online posting

"#FDA #Feedback Leads to Discontinuation of #Tesetaxel Development in Solid #Tumors https://t.co/KEKsVLzCpz via @targetedonc" (@TDTM2V)

FDA event • Oncology • Solid Tumor

"@PTarantinoMD cosa è successo al tesetaxel??? Il trial era stato presentato a dicembre negli USA e aveva dato risultati ottimi. Perché è stoppato ? Puoi aiutarmi? Grazie" (@GioCap75)

"$ODT Announces Discontinuation of Development of Tesetaxel. Will wind down the operations of the Company" (@BioStocks)