amcasertib (BBI-503) / Sumitomo Pharma - LARVOL DELTA

Suppressing liver metastasis growth by inducing the endogenous expression of the tumor suppressor miR-34a by small synthetic molecules (AACR 2025) - "However, when validating these compounds, only 6 (AT7519, A-674563, BBI503, PCM0240249, KRIBB and SB273005) out of 9 compounds that were tested -induced miR-34a promoter activation and only 2 (AT7519 and A-674563) out of the 6, also caused miR-34a secretion from HepG2, a human hepatoblastoma cell line. Induction of miR-34a using small synthetic molecules is a novel therapeutic approach to eradicate CRC liver metastasis."

Late-breaking abstract • Breast Cancer • Colorectal Cancer • Gastric Cancer • Hepatoblastoma • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • MIR34A

Novel marginal zone lymphoma models of resistance to the dual inhibition of PI3K and BCL2 (AACR 2024) - "Multi-drug resistance phenotype was ruled out by confirming sensitivity to vincristine...The response to MCL1-i, mTOR-i, and epigenetic agents (decitabine, HDAC, BET, and EZH2 inhibitors) was maintained. Triple combinations of copanlisib/venetoclax with the AURKA inhibitor alisertib, PLK inhibitor rigosertib, or the multikinase inhibitor amcasertib were active in both parental and resistant cells... We created four novel MZL-derived models of secondary resistance to PI3K and BCL2 inhibitors, which will help clarify possible modalities to overcome resistance. Novel potential targets were already identified, such as AURKA or PLK, to be further exploited."

IO biomarker • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • BCL2 • CD19 • CXCL13 • MCL1 • PIK3CA • PIK3CD

Cancer stemness kinase inhibitor amcasertib: a promising therapeutic agent in ovarian cancer stem and cancer cell models with different genetic profiles. (PubMed, Med Oncol) - "Furthermore, the suppression of Nanog-mediated stem cell-like features by Amcasertib was particularly pronounced in ER-negative ovarian cancer and cancer stem cells, highlighting its high anticancer efficacy in this subgroup. These results suggest that Amcasertib holds promise as a potential standalone or combination therapy agent for the treatment of ER-negative ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor • ER • NANOG

Comparison of Data from Fresh and Frozen AML Samples for Functional Drug Testing (ASH 2022) - "Samples that had been frozen were more sensitive to drugs such as kinase inhibitors (amcasertib, dinaciclib), as well as apoptotic modulators (S-63845), and proteasome inhibitors (VLX1570). Additionally, fresh samples were more sensitive to paclitaxel than frozen ones across the paired samples.The cell composition of paired samples was also affected by cryopreservation, with a reduction in the frequency of cells expressing c-KIT (CD117) and a reduction of cells with high granularity (side scatter)...However, careful consideration should be given to the specific drugs and cell populations of interest before deciding on sample handling methodology. This may be of particular importance when investigating specific drugs and phenotypes affecting cell proliferation and maturation stage, as sample handling may induce systematic differences and confound interpretation."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • ITGAM • KIT • NCAM1

A phase 1b/2 study of amcasertib, a first-in-class cancer stemness kinase inhibitor, in advanced adenoid cystic carcinoma. (ASCO 2017) - P1/2; "...Background: Amcasertib (BBI-503) is an oral first-in-class cancer stemness kinase inhibitor... Clinical safety and encouraging signs of anti-cancer activity were observed in pts with advanced ACC who received treatment with amcasertib. Long term follow-up demonstrates prolonged duration of disease control and that a majority of pts in this cohort have survived beyond 2 years. Further clinical evaluation of amcasertib in pts with ACC is warranted."

Clinical • Biosimilar • Oral Cancer

A phase 1b/2 study of amcasertib, a first-in-class cancer stemness kinase inhibitor in advanced head and neck cancer. (ASCO 2017) - P1/2; "...Background: Amcasertib (BBI-503) is an oral first-in-class cancer stemness kinase inhibitor... Clinical safety and encouraging signs of anti-cancer activity were observed in pts with advanced head and neck cancers who have received treatment with amcasertib. Objective response, prolonged disease control, and extended survival have been observed in this pre-treated population with a poor prognosis. Further clinical evaluation of amcasertib in patients with head and neck cancers is warranted."

Clinical • Biosimilar • Oral Cancer

A Study of BBI503 in Combination With Selected Anti-Cancer Therapeutics in Adult Patients With Advanced Cancer (clinicaltrials.gov) - P1 | N=165 | Completed | Sponsor: Sumitomo Dainippon Pharma Oncology, Inc | Phase classification: P1/2 ➔ P1

Combination therapy • Phase classification • Oncology • Solid Tumor

A Study of BBI503 in Combination With Selected Anti-Cancer Therapeutics in Adult Patients With Advanced Cancer (clinicaltrials.gov) - P1/2; N=165; Completed; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Oncology • Solid Tumor

A Study of BBI503 in Adult Patients With Advanced Hepatobiliary Cancer (clinicaltrials.gov) - P2; N=45; Completed; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Active, not recruiting ➔ Completed

Clinical • Trial completion • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

A Study of BBI503 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=320; Completed; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Active, not recruiting ➔ Completed; Phase classification: P1/2 ➔ P1; Trial completion date: Dec 2020 ➔ Jun 2020; Trial primary completion date: Jan 2020 ➔ Jun 2020

Clinical • Phase classification • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study of BBI608 in Combination With Sorafenib, or BBI503 in Combination With Sorafenib in Adult Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2; N=99; Completed; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Active, not recruiting ➔ Completed; Trial completion date: Aug 2020 ➔ Oct 2019

Clinical • Combination therapy • Trial completion • Trial completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Reperfusion Injury • Solid Tumor

A Study of BBI608 and BBI503 Administered in Combination to Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=147; Completed; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Active, not recruiting ➔ Completed

Clinical • Trial completion • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Study of BBI503 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: Boston Biomedical, Inc; Phase classification: P1 -> P1/2 ; N=50 -> 180 ; Trial primary completion date: Jun 2014 ->Jun 2015

Enrollment change • Phase classification • Trial primary completion date • Biosimilar • Oncology

BBI608-503-103HCC: A phase Ib/II clinical study of napabucasin (BBI608) in combination with sorafenib or amcasertib (BBI503) in combination with sorafenib (Sor) in adult patients with hepatocellular carcinoma (HCC). (ASCO 2017) - "In this phase Ib study, RP2D were determined for napabucasin and amcasertib to be safely combined with sorafenib at full dose, showing encouraging anti-tumor activity in patients with HCC who have not received prior systemic chemotherapy. A randomized phase II is schedule to start."

Combination therapy • Biosimilar • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Study of BBI608 and BBI503 Administered in Combination to Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Boston Biomedical, Inc; N=40 ➔ 120

Enrollment change • Biosimilar • Hepatocellular Cancer • Oncology

A Study of BBI503 in Asymptomatic Recurrent Ovarian Cancer Patients With CA-125 Elevation (clinicaltrials.gov) - P2; N=30; Active, not recruiting; Sponsor: Boston Biomedical, Inc; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Gynecologic Cancers • Oncology • Ovarian Cancer

A Study of BBI503 in Adult Patients With Advanced Urologic Malignancies (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: Boston Biomedical, Inc; Initiation date: Jan 2015 ➔ Jul 2016; Trial primary completion date: Jan 2016 ➔ Jul 2017

Trial initiation date • Trial primary completion date • Biosimilar • Oncology • Renal Cell Carcinoma

A Study of BBI608 in Combination With Sorafenib, or BBI503 in Combination With Sorafenib in Adult Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2; N=99; Active, not recruiting; Sponsor: Boston Biomedical, Inc; Trial primary completion date: Dec 2019 ➔ Jul 2019

Clinical • Combination therapy • Trial primary completion date

A Study of BBI503 in Combination With Selected Anti-Cancer Therapeutics in Adult Patients With Advanced Cancer (clinicaltrials.gov) - P1/2; N=165; Active, not recruiting; Sponsor: Boston Biomedical, Inc; Trial primary completion date: May 2019 ➔ Dec 2019

Clinical • Combination therapy • PD(L)-1 Biomarker • Trial primary completion date

A Study of BBI608 in Combination With Sorafenib, or BBI503 in Combination With Sorafenib in Adult Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2; N=99; Active, not recruiting; Sponsor: Boston Biomedical, Inc; Trial primary completion date: Dec 2018 ➔ Nov 2019

Clinical • Combination therapy • Trial primary completion date

A Study of BBI503 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=320; Active, not recruiting; Sponsor: Boston Biomedical, Inc; Trial primary completion date: Dec 2018 ➔ Mar 2020

Clinical • Trial primary completion date

A Study of BBI503 in Adult Patients With Advanced Gastrointestinal Stromal Tumors (clinicaltrials.gov) - P2; N=2; Terminated; Sponsor: Boston Biomedical, Inc; Active, not recruiting ➔ Terminated; Low feasibility

Clinical • Trial termination

A Study of BBI503 in Adult Patients With Advanced Urologic Malignancies (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Boston Biomedical, Inc; Trial primary completion date: Dec 2018 ➔ Aug 2018

Clinical • Trial primary completion date

Short-term organoid culture for drug sensitivity testing in high-grade serous ovarian cancer (SGO 2019) - "...Standard agents included oxaliplatin, paclitaxel, olaparib, and combinations for dual therapy. Targeted agents included mocetinostat, trametinib, LY294002, AZD5363, BBI503, MK1775, sorafenib, APR246, CB5083, and napabucasin... Short-duration organoid culture of MCS from HGSOC effusions can be used as a platform for empiric drug sensitivity testing. Using this model as a pretreatment ex vivo assessment of a drug's antitumor activity could be helpful in the selection of the most active agents for each patient."

Preclinical

Short-term organoid culture for drug sensitivity testing in high-grade serous ovarian cancer (SGO 2019) - "...Standard agents included oxaliplatin, paclitaxel, olaparib, and combinations for dual therapy. Targeted agents included mocetinostat, trametinib, LY294002, AZD5363, BBI503, MK1775, sorafenib, APR246, CB5083, and napabucasin... Short-duration organoid culture of MCS from HGSOC effusions can be used as a platform for empiric drug sensitivity testing. Using this model as a pretreatment ex vivo assessment of a drug's antitumor activity could be helpful in the selection of the most active agents for each patient."

Preclinical