vodobatinib (SCO - 088) / Sun Pharma Advanced Research Company - LARVOL DELTA

Combinatorial Treatment Options for Highly Resistant Compound Mutations in the Kinase Domain of the BCR: : ABL1 Fusion Gene (ASH 2023) - "The cells pre-tested in this way were exposed in vitro to different concentrations of various drugs including ponatinib combined with a number of other agents such as asciminib, hydroxyurea, palbociclib, venetoclax, ibrutinib, vodobatinib, and crizotinib...Overall, combinatorial treatment of BCR: : ABL1 CMs indicated that relatively low concentrations of the drugs used are capable of effectively inhibiting in vitro survival of mutant cells in most instances, which is important with regard to the expected toxicity of combinatorial treatment approaches. Since our earlier data indicated a good correlation between in vitro test results and clinical responses, our observations may serve as a basis for novel treatment options in patients with Ph +leukemias displaying challenging BCR: : ABL1 KD-mutations."

Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Validation of a Dried Blood Spot Method for the Determination of a Third-Generation Bcr-Abl 1 Inhibitor, Vodobatinib, in Small Volumes of Rat Blood: Application to a Pharmacokinetic Study. (PubMed, Biomed Chromatogr) - "For intravenous dosing, AUC0-∞ was 9475 ng·h/mL (DBS) versus 10,109 ng·h/mL (plasma), and for oral dosing, Cmax values were 568 ng/mL (DBS) versus 544 ng/mL (plasma). Oral bioavailability was nearly identical between matrices (98.7% for DBS vs. 97.9% for plasma), confirming the reliability of DBS sampling for PK studies of vodobatinib."

Journal • PK/PD data • Preclinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial. (PubMed, Lancet Haematol) - P1/2 | "Pooled analysis of the phase 1 and 2 studies showed clinically meaningful antileukaemic activity of vodobatinib and a tolerable safety profile in patients with advanced chronic myeloid leukaemia who previously received multiple TKIs, including ponatinib and asciminib, addressing an otherwise unmet clinical need. The phase 2 study was statistically underpowered and warrants further investigation in a phase 3, randomised controlled trial and in an earlier treatment setting of the disease."

Journal • P1/2 data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pulmonary Disease • Thrombocytopenia • ABL1

Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial (Lancet Haematol) - P1/2 | N=122 | NCT02629692 | Sponsor: Sun Pharma Advanced Research Company Limited | "At data cutoff, major cytogenetic response was observed in 44 (70%) of 63 patients with chronic-phase chronic myeloid leukaemia, of which 12 (75%) of 16 patients in the phase 2 study had major cytogenetic response. For patients with accelerated-phase chronic myeloid leukaemia, six (86%) of seven patients had a major haematological response (median duration 17·8 [IQR 10·2–24·3]) at data cutoff; major haematological response was observed in three (100%) evaluable patients in the phase 2 study. Major haematological response was reached by two (50%) of four patients with blast-phase chronic myeloid leukaemia and the median duration of response was 6·2 months (IQR 3·2–9·3); no blast-phase patients were enrolled in the phase 2 study."

P1/2 data • Chronic Myeloid Leukemia

Vodobatinib overcomes cancer multidrug resistance by attenuating the drug efflux function of ABCB1 and ABCG2. (PubMed, Eur J Pharmacol) - "Overall, our findings unveil an additional pharmacological facet of vodobatinib against ABCB1 and ABCG2 activity, suggesting its potential incorporation into combination therapy for a specific subset of patients with tumors characterized by high ABCB1 or ABCG2 levels. Further investigation is warranted to fully elucidate the clinical implications of this therapeutic approach."

Journal • Oncology • ABCB1 • ABCG2 • ABL1

Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment of Ph+ CML Resistant/Intolerant to ≥3 Prior CML Therapies (clinicaltrials.gov) - P1/2 | N=122 | Active, not recruiting | Sponsor: Sun Pharma Advanced Research Company Limited | Recruiting ➔ Active, not recruiting | N=303 ➔ 122 | Trial primary completion date: Jan 2026 ➔ Aug 2026

Enrollment change • Enrollment closed • Trial primary completion date • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Efficacy and Safety of Vodobatinib in Patients (pts) with Chronic Phase Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML): A Sub Group Analysis By Lines of Tyrosine Kinase Inhibitor (TKI) Therapy (ASH 2022) - P1/2 | "Vodobatinib demonstrated efficacy and safety in 2T and 3T pts (including pts treated with ponatinib and asciminib) and is well tolerated. Vodobatinib remains a potential option for these highly refractory pts. A phase 2 study (NCT02629692) of vodobatinib is currently ongoing in CML pts failing ≥ 3 TKI including ponatinib."

Clinical • Anemia • Cardiovascular • Cerebral Hemorrhage • Chronic Myeloid Leukemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Leukemia • Musculoskeletal Pain • Neutropenia • Novel Coronavirus Disease • Oncology • Pain • Thrombocytopenia

Management of Chronic Myeloid Leukemia Patients in Later Lines: The Role of Ponatinib and New Compounds. (PubMed, Clin Lymphoma Myeloma Leuk) - "Recently approved by FDA, the first-of-its-kind STAMP inhibitor asciminib has proven safe and effective, obtaining deep and stable molecular responses even in heavily pretreated patients and with T315I mutation...Among these, novel agents such as vodobatinib and olverembatinib have provided promising result in clinical trials, representing valuable therapeutic possibilities in intolerant or refractory patients. Therefore, a more complex therapeutic paradigm is expected in the near future."

Journal • Review • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Vodobatinib in CML (CML-MPN 2023) - No abstract available

"Great presentation by ⁦@GCC_Cortes⁩ on #vodobatinib in #cml. Great live updates on #worldcup2022 at the beginning of the presentation. 👏 👏 https://t.co/K8c1ZE7YLx #ASH22" (@AlkaliDr)

Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment Refractory/Intolerant CML Failing ≥3 Prior CML Therapies (clinicaltrials.gov) - P1/2 | N=303 | Recruiting | Sponsor: Sun Pharma Advanced Research Company Limited | Trial primary completion date: Aug 2022 ➔ Jan 2026

Trial primary completion date • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

An Update of Safety and Efficacy Results from Phase 1 Dose-Escalation and Expansion Study of Vodobatinib, a Novel Oral BCR-ABL1 Tyrosine Kinase Inhibitor (TKI), in Patients with Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Failing Prior TKI Therapies (ASH 2021) - P1/2 | "Vodobatinib continues to be associated with favourable long term safety and efficacy in heavily pre-treated CML failing ≥ 3 prior TKIs, including ponatinib. Phase 2 study evaluating vodobatinib in pts failing at least 3 prior lines of therapy, including ponatinib, is ongoing."

Clinical • P1 data • Acute Lymphocytic Leukemia • Anemia • Atherosclerosis • Back Pain • Cardiovascular • Cerebral Hemorrhage • Chronic Myeloid Leukemia • CNS Disorders • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertension • Hypotension • Immunology • Infectious Disease • Leukemia • Musculoskeletal Pain • Neutropenia • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Respiratory Diseases • Thrombocytopenia • ABL1 • BCR

CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions. (PubMed, Curr Hematol Malig Rep) - "Results of novel TKIs have been recently reported, especially for the setting of T315I mutated patients, such as olverembatinib and asciminib, or for patients who developed resistance due to other mutations, such as vodobatinib...New potential treatments are on the horizon in the field of CML, able to rescue patients treated firstly with one or more second-generation TKIs. Results of ongoing trials and real-world evidence dataset will help us to identify the appropriate timing of intervention and to select appropriate candidate to these drugs."

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Vodobatinib in chronic phase Ph+ CML - updated efficacy results (ESH-CML 2022) - No abstract available

Clinical

SPARC to present updated clinical data of vodobatinib at the 63rd ASH annual meeting (Pharmabiz) - "The phase 1 study outcomes will be presented by Professor. Jorge Cortes...on Saturday,11th December, 2021. Results from the ongoing vodobatinib clinical study are being presented for the second consecutive year at the ASH annual meeting, underlining the promising potential of vodobatinib for the treatment of heavily pre-treated CML."

Regulatory

"新規チロシンキナーゼ阻害薬の #vodobatinib は、ポナチニブを含む3剤以上のTKI治療歴を有する #慢性骨髄性白血病 （ #CML ）とPh+の #急性リンパ芽球性白血病 （ #ALL ）に持続的な効果を示すことが #ASH21 で発表されました。 https://t.co/or4CZDzFyx" (@cancer_navi)

Novel BCR-ABL1 tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. (PubMed, Expert Rev Hematol) - No abstract available

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Phase 1 Trial of K0706, a Novel Oral BCR-ABL1 Tyrosine Kinase Inhibitor (TKI): In Patients with Chronic Myelogenous Leukemia (CML) and Phildelphia Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Failing ≥ 3 Prior TKI Therapies: Initial Safety and Efficacy (ASH 2019) - P1/2; "Introduction: Despite availability of several BCR-ABL1 TKIs for treatment of CML, some patients (pts) fail ≥3 TKIs and/or have co-morbidities that limit use of 2nd generation TKIs (2GTKI: Nilotinib, Dasatinib and Ponatinib). K0706 has acceptable safety profile with activity in heavily pre-treated patients who had failed at least ≥3 prior lines of TKIs. The study provides early proof of principle for the effectiveness of K0706 in a setting with few available treatment options."

Clinical • P1 data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pain • Thrombocytopenia • ABL1

Dr. Cortes on Emerging Therapies in CML (OncLive) - "Jorge E. Cortes, MD...discusses emerging therapies in chronic myeloid leukemia (CML)....Additionally, other novel agents, including the BCR-ABL TKIs vodobatinib (K0706), HQP1351, and PF-114, have demonstrated early efficacy signals in CML and are under further investigation in phase 2 studies, Cortes concludes."

Video

K0706 for Patients Diagnosed With Dementia With Lewy Bodies (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Georgetown University; Trial completion date: Aug 2021 ➔ Oct 2023; Trial primary completion date: Jan 2021 ➔ Jun 2023

Clinical • Clinical data • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease

[VIRTUAL] Prevalence of Sars-Cov-2 Infection in Patients with Chronic Myeloid Leukemia (ASH 2020) - "Twenty pts were off TKI (post-alloSCT, n=12; in treatment free remission n=6; pregnancy=1 and intolerance n=1) and 141 were on active treatment (imatinib [n=41], dasatinib [n=38], nilotinib [n=23], bosutinib [n=21], asciminib [n=11], ponatinib [n=6] and K0706 [n=1])...The only patient with severe COVID-19 developed pneumonia requiring CPAP, was refractory to tocilizumab (anti-IL6), but recovered after starting ruxolitinib (JAK2-inhibitor)...Of note is the higher prevalence in the BAME community and underlines the potential role of socioeconomic factors in disease transmission. Expansion of this CML cohort and serial antibody testing in seropositive patients will provide further information regarding prevalence and durability of serological responses."

Clinical • Chronic Myeloid Leukemia • Fatigue • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Musculoskeletal Pain • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Respiratory Diseases • Solid Tumor • Thrombosis

CML: New TKIs and combos show promise for resistant, intolerant disease (MDedge Hematology & Oncology) - "The allosteric inhibitor asciminib (ABL-001), for example, has completed phase 1/2 trials evaluating its use as a single agent and in combination with other therapies in the first-line setting, and a pivotal phase 3 study comparing it with bosutinib in the third-line setting is underway, Dr. Cortes said....'It is important that we have new therapeutic options to be able to help these patients who are going to be in need of additional therapies,' he said."

Media quote

Highlights in Chronic Myeloid Leukemia From ASH 2020 (Medscape) - "Dr Cortes also reports on two new drugs, HQP1351 (olverembatinib) and K0706 (vodobatinib), both reporting very high response rates in treating resistance to first- and second-generation TKIs. Ponatinib, another novel treatment, shows high response rates and survival outcomes in patients who have had no success with second-generation TKIs. Finally, the first-ever randomized study comparing the success rate of two frontline TKIs, nilotinib and dasatinib, is presented."

Video

PROSEEK: A Phase 2 Study In Early Parkinson's Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706 (clinicaltrials.gov) - P2; N=504; Recruiting; Sponsor: Sun Pharma Advanced Research Company Limited; Trial completion date: Feb 2021 ➔ Mar 2023

Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

K0706 for Patients Diagnosed With Dementia With Lewy Bodies (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Georgetown University; Active, not recruiting ➔ Recruiting

Clinical • Clinical data • Enrollment open • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease