Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial.

Purpose: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study.

Methods: Adults with disease progression on previous therapies were eligible.

Phase 1 study of DS-1205c combined with gefitinib for EGFR mutation-positive non-small cell lung cancer.

Background: Tyrosine kinase inhibitors (TKIs) are effective for the treatment of non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR), but responses are not durable as tumors develop resistance. DS-1205c is a novel, specific, orally bioavailable, small-molecule AXL receptor TKI. In preclinical studies, DS-1205c restored TKI antitumor activity in a TKI acquired-resistance EGFR-mutant NSCLC tumor xenograft model.

Safety and Efficacy of Mirogabalin for Peripheral Neuropathic Pain: Pooled Analysis of Two Pivotal Phase III Studies.

Purpose: Mirogabalin besylate has been approved in several countries to treat peripheral neuropathic pain. This pooled analysis, using data from the two pivotal Phase III studies in Asian patients with diabetic peripheral neuropathic pain and post-herpetic neuralgia, aimed to provide clinicians with more detailed and precise information relating to mirogabalin's safety and efficacy.

Methods: Data were pooled from 2 multicenter, double-blind, placebo-controlled, parallel-group, 14-week treatment studies of mirogabalin conducted at ∼350 study sites (Japan, South Korea, Taiwan, Singapore, Malaysia, and Thailand).

Concentration-QTc analysis for single arm studies.

Concentration-QTc (C-QTc) modeling is being increasingly used in phase 1 studies. For studies without a placebo arm (single arm studies), the scientific whitepaper by Garnett et al. ( https://doi.

Long-term safety and efficacy of mirogabalin in Asian patients with postherpetic neuralgia: Results from an open-label extension of a multicenter randomized, double-blind, placebo-controlled trial.

Objective: Postherpetic neuralgia (PHN) is a condition that results from nerve dysfunction following an episode of acute herpes zoster (shingles). Mirogabalin is a novel, selective oral α2δ ligand that demonstrated safety and efficacy in a multicenter, randomized, double-blind, placebo-controlled 14-week study in Asian patients with PHN. This 52-week, open-label extension study investigated the long-term safety and efficacy of flexible-dosage mirogabalin in Asian patients with PHN.

Mirogabalin in Japanese Patients with Renal Impairment and Pain Associated with Diabetic Peripheral Neuropathy or Post-Herpetic Neuralgia: A Phase III, Open-Label, 14-Week Study.

Purpose: Mirogabalin was recently approved in Japan for the treatment of peripheral neuropathic pain, based on data from clinical trials in diabetic peripheral neuropathic pain (DPNP) and post-herpetic neuralgia (PHN), common clinical conditions which cause intense distress for patients. We characterized the safety and tolerability of mirogabalin in Japanese patients with renal impairment.

Patients And Methods: This multicenter, open-label study (ClinicalTrials.

Results of Mirogabalin Treatment for Diabetic Peripheral Neuropathic Pain in Asian Subjects: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Study.

Introduction: Almost one-quarter of Asian patients with diabetes experience diabetic peripheral neuropathic pain (DPNP), which may be associated with moderate or severe levels of pain, insomnia, mood disorders, and worsened quality of life. Current treatments are generally ineffective and may be poorly tolerated. We evaluated mirogabalin as a treatment for DPNP in Asian subjects.

Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.

Aims/introduction: Diabetic peripheral neuropathic pain (DPNP) affects the functionality, mood and sleep patterns of patients with diabetes. Mirogabalin, an α δ ligand with a slower dissociation for α δ-1 versus α δ-2 subunits, showed efficacy and safety in a randomized, double-blind, placebo-controlled, 14-week study in Asian patients with DPNP. This open-label extension study evaluated the long-term safety and efficacy of mirogabalin in Asian patients with DPNP.

Efficacy and safety of quizartinib in Japanese patients with FLT3-ITD positive relapsed or refractory acute myeloid leukemia in an open-label, phase 2 study.

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations in patients with acute myeloid leukemia (AML) are associated with early relapse and poor survival. This multicenter, single-arm, two-stage phase 2 study (NCT02984995) was conducted to evaluate the efficacy and safety of quizartinib hydrochloride (initial dose 20/30 mg/day), an oral, highly potent, selective FLT3 inhibitor in Japanese patients (median age 65 years) with FLT3-ITD positive relapsed/refractory (R/R) AML. The composite complete remission (CRc) rate (primary endpoint) was 53.

Safety and pharmacokinetics of quizartinib in Japanese patients with relapsed or refractory acute myeloid leukemia in a phase 1 study.

Expanded therapeutic options are warranted for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations. The present phase 1, multicenter, open-label, dose-escalation and dose-expansion study was conducted to assess the safety, pharmacokinetics, and efficacy of multiple-dose monotherapy of the FLT3 inhibitor, quizartinib, in Japanese patients with R/R AML. Patients received oral quizartinib, once daily, under fasting conditions in 28-day cycles.

Mirogabalin for the management of postherpetic neuralgia: a randomized, double-blind, placebo-controlled phase 3 study in Asian patients.

This study investigated the safety and efficacy of mirogabalin, a novel, potent, selective ligand of the α2δ subunit of voltage-dependent Ca channels, for the treatment of postherpetic neuralgia (PHN). In this multicenter, double-blind, placebo-controlled phase 3 study, Asian patients ≥20 years with PHN were randomized 2:1:1:1 to placebo or mirogabalin 15, 20, or 30 mg/day for up to 14 weeks (NCT02318719). The primary efficacy endpoint was the change from baseline in average daily pain score at week 14, defined as a weekly average of daily pain (0 = "no pain" to 10 = "worst possible pain," for the last 24 hours).

Mirogabalin for the treatment of diabetic peripheral neuropathic pain: A randomized, double-blind, placebo-controlled phase III study in Asian patients.

Aims/introduction: This study evaluated the efficacy and safety of mirogabalin, a novel, potent, selective ligand of the α δ subunit of voltage-dependent Ca channels, for the treatment of diabetic peripheral neuropathic pain (DPNP).

Materials And Methods: During this double-blind, multisite, placebo-controlled phase III study, Asian patients aged ≥20 years with type 1 or 2 diabetes and DPNP were randomized 2:1:1:1 to a placebo, mirogabalin 15, 20 or 30 mg/day for up to 14 weeks, with a 1- to 2-week titration (NCT02318706). The primary endpoint was the change from baseline in average daily pain score (ADPS) at week 14, defined as a weekly average of daily pain (0 = no pain to 10 = worst possible pain, for the past 24 h).

Tolerability, pharmacokinetics, and pharmacodynamics of mirogabalin in healthy subjects: Results from phase 1 studies.

Three phase 1 pharmacokinetic (PK)/pharmacodynamics (PD) studies were conducted in healthy men and women to further characterize the safety, tolerability, and PK/PD of mirogabalin administration with or without food and to guide the dose selection and regimen for phase 2 and 3 clinical development. The 3 studies included 2 randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose studies, and 1 open-label, crossover study to evaluate the PK of mirogabalin administered under fasting and fed (high-fat meal) conditions. Forty-eight and 47 healthy volunteers completed the single- and multiple-dose studies, respectively.

A Randomized, Placebo-Controlled, Double-Blind Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeated Doses of Mirogabalin in Healthy Asian Volunteers.

Mirogabalin is a novel, preferentially selective α δ-1 ligand under investigation to treat neuropathic pain. The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of various doses of mirogabalin in healthy subjects of different ethnicities. This randomized, placebo-controlled, double-blind, sequential, ascending-dose study evaluated single (10-40 mg) and repeated (10, 15 mg twice a day) doses of mirogabalin in Japanese subjects, and a single dose of mirogabalin in Korean, Chinese, and white subjects.

Phase 1 study of new formulation of patritumab (U3-1287) Process 2, a fully human anti-HER3 monoclonal antibody in combination with erlotinib in Japanese patients with advanced non-small cell lung cancer.

Background: This phase 1 study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287) Process 2, a new formulation of fully human anti-HER3 monoclonal antibody in combination with erlotinib, an epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) in prior chemotherapy treated Japanese patients with advanced non-small cell lung cancer (NSCLC).

Methods: Patients received intravenous patritumab Process 2 formulation at 9 mg/kg every 3 weeks after initiation of 18 mg/kg loading dose combined with continuous daily dose of erlotinib (150 mg QD) until any of the withdrawal criteria are met. Adverse events (AEs) were assessed using CTCAE v4.

Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.

Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer.

Bayesian adaptive patient enrollment restriction to identify a sensitive subpopulation using a continuous biomarker in a randomized phase 2 trial.

With the development of molecular targeted drugs, predictive biomarkers have played an increasingly important role in identifying patients who are likely to receive clinically meaningful benefits from experimental drugs (i.e., sensitive subpopulation) even in early clinical trials.