Fujovee (abivertinib) / Sorrento - LARVOL DELTA

Drug-drug interactions between epidermal growth factor receptor tyrosine kinase inhibitors and rivaroxaban in vitro and in vivo. (PubMed, PLoS One) - "These findings confirm the presence of DDIs between EGFR TKIs and rivaroxaban. Avitinib and gefitinib significantly inhibit rivaroxaban metabolism, and their co-administration may aggravate the risk of bleeding."

Journal • Preclinical • Cardiovascular • Oncology • Venous Thromboembolism • CYP3A4 • EGFR

Genome-wide CRISPR-Cas9 screening identifies ITGA8 responsible for abivertinib sensitivity in lung adenocarcinoma. (PubMed, Acta Pharmacol Sin) - "This study demonstrates that ITGA8 inhibits the proliferation, invasion and migration of lung adenocarcinoma cells, enhances the sensitivity to EGFR-TKIs, improves treatment efficacy, and delays the progression of acquired resistance. Thus, ITGA8 presents a potential therapeutic candidate for addressing acquired resistance to EGFR-TKIs from a novel perspective."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Practical Application of Orelabrutinib in Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Analysis of Real-World Evidence (OCARE Study) (ASH 2024) - "20.8% (16/77) of the patients who had previously been treated with BTK inhibitors, including ibrutinib, zanubrutinib, avitinib and SS-001, switched to orelabrutinib due to AE intolerance or unsatisfactory efficacy.Median follow-up time was 9.8 months (range, 0.7-25.7). No unexpected adverse events were reported.Conclusion : The study demonstrates that orelabrutinib elicits robust hematological responses in both newly diagnosed and relapsed/refractory CLL/SLL patients, with an acceptable safety profile and a prolonged DOT. Although limited by its sample size, the data provide compelling evidence that orelabrutinib is a promising therapeutic option for CLL/SLL patients."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Leukopenia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • IGH • TP53

Genome-wide CRISPR-Cas9 Screening Identifies ITGA8 Responsible for Abivertinib Sensitivity in Lung Adenocarcinoma (IASLC-WCLC 2024) - "Conclusions : ITGA8 reduces the proliferation, invasion, and migration capabilities of tumor cells, enhances the sensitivity of lung adenocarcinoma to EGFR-TKIs, improves treatment efficacy, and prolongs the duration of acquired resistance. ITGA8 is a potential therapeutic target that may address acquired resistance to EGFR-TKIs from a novel perspective."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Development and validation of a deep learning-based model to predict response and survival of T790M mutant non-small cell lung cancer patients in early clinical phase trials using electronic medical record and pharmacokinetic data. (PubMed, Transl Lung Cancer Res) - "We utilized the electronic medical record (EMR) and pharmacokinetic parameters of 326 T790M-mutated NSCLC patients, including 283 patients treated with Abivertinib in phase I (n=177, for training) and II (n=106, for validation) clinical trials and an additional validation cohort 2 comprising 43 patients treated with BPI-7711. CoxMoE offers a valuable approach for patient selection by forecasting therapeutic response and PFS utilizing laboratory tests and pharmacokinetic parameters in the setting of early-phase clinical trials. Simultaneously, CoxMoE could predict the efficacy of third-generation EGFR-TKI non-invasively for T790M-positive NSCLC patients, thereby complementing existing EGFR genotype detection."

Journal • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Abivertinib Shows Promise Treating Marginal Zone Lymphoma (Pharmacy Times) - P1/2a | N=184 | NCT03060850 | Hangzhou ACEA Pharmaceutical Research Co., Ltd. | "Abivertinib...produced promising results in patients with relapsed/refractory marginal zone lymphoma...The study found that patients with relapsed/refractory MZL (n = 27) previously administered multiple lines of therapy experienced an overall response rate (ORR) of 59.3% with abivertinib, including a complete response rate of 11.1% and a partial response rate of 48.2%. Further, the disease control rate (DCR) was 92.6%, while median progression-free survival (PFS) and duration of response had not yet been reached...A previously conducted phase 1 portion of the trial with a data cutoff date of August 28, 2020, showed that abivertinib produced an ORR of 54.2% and a DCR of 95.8% across all doses in patients with relapsed/refractory B-cell lymphomas...The phase 2a portion of the trial did not find any instances of severe bleeding, arrhythmia, or hypertension..."

P1/2 data • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

Sorrento Announces Positive Phase IIa Study Results of Abivertinib for the Treatment of Relapsed/Refractory Marginal Zone Lymphoma (R/R MZL) and Its Plan for a Pivotal Phase III Study (GlobeNewswire) - P2a | N=27 | "Sorrento Therapeutics...announced positive results from a China phase IIa study of Abivertinib on R/R MZL and its plan for a pivotal study....The phase IIa study on R/R MZL, a rare type of B cell lymphoma, was conducted in China in 27 R/R MZL patients. Abivertinib showed significant treatment benefits in 27 patients who were relapsed or refractory after multiple lines of treatment with an ORR of 59.3% (11.1% CR and 48.2% partial responses). This ORR is higher than the ORR of Ibrutinib (46%), which was first approved for the treatment of R/R MZL.(3) The DCR was 92.6% and to date, both PFS and DOR have not been reached....Sorrento has communicated with the NMPA, and a consensus has been reached for a pivotal phase III registration study for the treatment of R/R MZL. The pivotal study will be a multicenter phase III study to assess the efficacy and safety of Abivertinib for treatment of relapsed/refractory marginal zone lymphoma."

New P3 trial • P2a data • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The Maverick trial: A phase 2 study of abivertinib in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). (ASCO 2023) - P2 | "Pts receive continuous treatment with abivertinib 200 mg BID with abiraterone 1000 mg QD + prednisone 5 mg BID until radiographic progression, unacceptable toxicity, intercurrent illness, or other reason, such as subject withdrawal. Trial Registration: NCT05361915 Funding Source: Sorrento Therapeutics, Inc, the trial’s sponsor who is funding the trial. Clinical trial information: NCT05361915."

Clinical • Metastases • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BTK • EGFR • HSD3B1

Evaluating the efficacy and cardiotoxicity of EGFR-TKI AC0010 with a novel multifunctional biosensor. (PubMed, Microsyst Nanoeng) - "This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated. In addition, novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds."

Journal • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Maverick: Study to Assess Abivertinib in Combination With Abiraterone in Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=100 | Suspended | Sponsor: Sorrento Therapeutics, Inc. | Recruiting ➔ Suspended

Combination therapy • Metastases • Trial suspension • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HSD3B1

Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice. (PubMed, BMC Pulm Med) - "At present, only two drugs are approved by the FDA for the treatment of IPF, including the synthetic pyridinone drug, pirfenidone, and the tyrosine kinase inhibitor, nintedanib. The cellular experiments also indicated that avitinib improved alveolar epithelial cell injury in A549 cells. In conclusion, the present findings demonstrated that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • SMAD3 • TGFB1

BMX inhibition and HSD3B1-driven resistance in prostate cancer in the Maverick trial. (ASCO-GU 2023) - P2 | "Multiple clinical studies demonstrate that adrenal-permissive HSD3B1 allele inheritance confers more rapid progression on ADT and others also suggest worse CRPC outcomes even after treatment with abiraterone or enzalutamide...BMX inhibition using zanubrutinib suppresses CRPC growth in the C4-2 and VCaP xenograft models by blocking intratumoral androgen synthesis and tumor androgen receptor (AR) signaling...All patients will receive treatment with abivertinib 200mg twice daily with abiraterone 1000mg daily and prednisone 5mg by mouth twice daily... BMX is required for 3βHSD1 phosphorylation, androgen biosynthesis and CRPC progression with the adrenal-permissive HSD3B1(1245C) allele. The Maverick trial will test clinical proof-of-concept of BMX inhibition in men with adrenal-permissive HSD3B1(1245C) inheritance. Clinical trial information: NCT05361915."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HSD3B1

Maverick: Study to Assess Abivertinib in Combination With Abiraterone in Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Sorrento Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HSD3B1

Maverick: Study to Assess Abivertinib in Combination With Abiraterone in Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Sorrento Therapeutics, Inc. | Initiation date: Oct 2022 ➔ Mar 2023

Combination therapy • Metastases • Trial initiation date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HSD3B1

Trial to evaluate TKI and abiraterone treatment combination for prostate cancer (Urology Times) - "MAVERICK, a phase 2, open-label clinical trial (NCT05361915) to evaluate the efficacy of a new prostate cancer treatment combination of abivertinib and abiraterone acetate (Zytiga), is now underway across 9 sites in the US....The treatment combination was based on findings from research that investigated the process through which prostate cancer synthesizes androgens. Results showed that a tyrosine kinase called BMX interacted with the enzyme produced by HSD2B1....Further research with preclinical models found that knocking out BMX or halting phosphorylation stopped androgen production and cancer growth. These findings identified BMX as the therapeutic target, resulting in the therapy combination in MAVERICK."

Preclinical • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer

Identification of LRRK2 Inhibitors through Computational Drug Repurposing. (PubMed, ACS Chem Neurosci) - "The experimental results showed six drugs (Abivertinib, Aumolertinib, Encorafenib, Bosutinib, Rilzabrutinib, and Mobocertinib) with IC less than 5 μM that were identified as potential LRRK2 kinase inhibitors. In summary, the results showed that our drug repurposing workflow could be used to identify potent compounds for LRRK2. The potent inhibitors discovered in our work can be a starting point to develop more effective LRRK2 inhibitors."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Sorrento Therapeutics to Participate in Key Opinion Leader Panel Discussion on “New Horizons for the Treatment of Non-small Cell Lung Cancer” (GlobeNewswire) - "Sorrento Therapeutics, Inc...announced that Dr. Mike A. Royal, Chief Medical Officer, will participate in an upcoming Key Opinion Leader (KOL) Panel Discussion that will focus on the great unmet need in non-small cell lung cancer and the potential of abivertinib, a novel, third-generation, EGFR/BTK inhibitor."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Overview of the multifaceted resistances toward EGFR-TKIs and new chemotherapeutic strategies in non-small cell lung cancer. (PubMed, Biochem Pharmacol) - "However, patients treated with third-generation TKIs (osimertinib, avitinib and rociletinib) targeting the EGFR T790M mutation have shown emerging resistances and relapses. This will pave the way for designing novel and effective chemotherapies to improve patients' overall survival. In this review, we provide an overview of the multifaceted mechanism of resistances towards EGFR-TKIs, as well as the challenges and perspectives that should be addressed in strategising chemotherapeutic treatments to overcome the ever evolving and adaptive nature of NSCLC."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Sorrento Announces Significant Positive Pivotal Trial Results as Assessed by an Independent Review Committee (IRC) With Matured Long-Term (Over Three Years) Follow-Up Data of Abivertinib for the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) (GlobeNewswire) - P1/2 | N=368 | NCT02330367 | Sponsor: Hangzhou ACEA Pharmaceutical Research Co., Ltd | "In these IRC-assessed preliminary topline results with more matured long-term follow up data (previously 16.8 months, now 38.8 months), Abivertinib showed significant treatment benefits in 209 response evaluable, heavily treated NSCLC patients with ORR of 56.5%, and notably a significant CR rate was seen with Abivertinib (5.3%) in comparison with that of osimertinib (Tagrisso) (0.5%)*, while the ORR rate is comparable between the two drugs. This combined data, the ORR of 56.5%, the CR rate of 5.3%, and median OS of 28.2 month (versus Tagrisso’s median OS of 26.8 months), is potentially superior to that of the approved third generation EGFR inhibitor (osimertinib)...Based on these results, Sorrento is closing the study and preparing the pre-NDA materials and NDA package."

P1/2 data • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study. (PubMed, Clin Cancer Res) - "Abivertinib of 300 mg BID demonstrated favorable clinical efficacy with manageable side-effects in patients with EGFR T790M+NSCLC."

Clinical • Journal • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Sorrento Announces Publication of Significant Positive Pivotal Trial Results of Abivertinib for the Treatment of Non-Small Cell Lung Cancer (NSCLC) in the Peer-Reviewed Journal Clinical Cancer Research (GlobeNewswire) - P1/2 | N=367 | "Sorrento Therapeutics, Inc. (Nasdaq: SRNE, 'Sorrento') today announced the peer-reviewed publication of significant results from a pivotal study of abivertinib on 227 heavily pretreated NSCLC patients in the journal Clinical Cancer Research, authored by Dr. Yi-Long Wu...Among 209 response evaluable patients, confirmed ORR was 52.2% (109/209; 95% CI: 45.2%, 59.1%) and the DCR was 88.0% (184/209, 95% CI: 82.9%, 92.1%). The median DoR and PFS were 8.5 months (95% CI: 6.1, 9.2) and 7.5 months (95% CI: 6.0, 8.8), respectively. The median OS was 24.9 months (95% CI: 22.4, NR). All patients (N=227) reported at least 1 AE, with 96.9% (220/227) reporting treatment-related AEs...Death was reported in 4.4% (10/227) of patients, and none was deemed related to abivertinib....Sorrento is conducting an independent review process with long-term follow up data and intends to request a pre-NDA meeting with FDA."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Sorrento Announces FDA Authorization to Proceed With Phase 2 Study of Abivertinib (Fujovee) to Treat Metastatic Castrate Resistant Prostate Cancer (MAVERICK Trial) (GlobeNewswire) - "Sorrento Therapeutics, Inc...announced that it has received clearance from the FDA for its investigational new drug application (IND) for Abivertinib (Fujovee™) for the Phase 2 MAVERICK study to be conducted in participants with metastatic castrate resistant prostate cancer (mCRPC) at multiple centers in the United States. The MAVERICK study will be conducted in a partnership with the Prostate Cancer Clinical Trials Consortium and will enroll participants with both abiraterone-naïve and abiraterone-progressing mCRPC....The primary objective of the study is to evaluate the efficacy of Abivertinib with abiraterone via an assessment of 6-month radiographic progression-free survival (rPFS) and the primary endpoint is the 6-month rPFS defined as a percent of subjects alive and without progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for measurable disease and Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases."

Clinical protocol • IND • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Beyond osimertinib: The development of 3-generation EGFR Tyrosine Kinase Inhibitors. (PubMed, J Thorac Oncol) - P3 | "In this review, we profiled many of the third-generation EGFR TKIs in late stage clinical development (e.g. almonertinib, lazertinib, alflutinib, rezivertinib, ASK120069, SH-1028, D-0316 and abivertinib) of their interim results of phase 1-3 trials and their chemical structures when publicly available. Additionally, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, maverlertinib) including phase 3 results of rociletinib and naquotinib. We further profiled the next-generation combination clinical trial design of third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704) and ACROSS2 (NCT04500717)."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Study to Assess Abivertinib in Combination With Abiraterone in Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Sorrento Therapeutics, Inc.

Combination therapy • New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HSD3B1

Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking. (PubMed, Netw Model Anal Health Inform Bioinform) - "Strong ligand-protein interactions were predicted among some of these drugs, that included: Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. It is also worth highlighting the powerful immunomodulatory role of other drugs, such as Abivertinib that inhibits pro-inflammatory cytokine production associated with cytokine release syndrome (CRS) and the progression of COVID-19 infection. The potential role of other Abl kinase inhibitors, including Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS), indicate that this drug may be useful for COVID-19, as the SARS-CoV-2 genome is similar to SARS-CoV."

Journal • Acute Respiratory Distress Syndrome • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases