This week on Pipeline Moves, we kick off by looking at the terminations of Phase II trials in metastatic hepatocellular carcinoma and thymic carcinoma, and a Phase I/II trial in Gaucher disease. On a good note, we investigate the completion of a Phase I/II trial in diabetic nephropathy and a Phase I trial in splenic marginal zone B cell lymphoma.Interested in more news in your inbox? Sign-up for our daily newsletter.
Bristol-Myers’ Phase II oncology trial termination
Bristol-Myers Squibb’s linrodostat mesylate saw its Phase Transition Success Rate (PTSR) drop in metastatic hepatocellular carcinoma (HCC) after a Phase II trial termination. The PTSR dropped by 11 points settling at 10%. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
On 22 August, the Phase II trial’s (NCT03695250) status on ClinicalTrials.gov changed from active, not recruiting to terminated [Funding source decision to terminate study] GlobalData evaluated the asset one day later.
The interventional, open-label, dose-response trial assessed Bristol-Myers Squibb’s candidate (also known as BMS-986205) in combination with nivolumab in subjects with HCC. A total of eight participants were enrolled in the study.
Linrodostat mesylate works by inhibiting Indoleamine 2,3-Dioxygenase 1 (IDO1), an enzyme important in tumor immune evasion. The candidate helps delay tumor cell growth by restoring the prognostic benefit of T cells.
Phase I/II Gaucher disease trial termination
AvroBio’s AVR-RD-02 (lentiviral-based gene therapy) saw its PTSR decrease in Gaucher disease type I after a Phase I/II trial in that indication was terminated. The drug’s PTSR dropped by 20 points, reaching 31% in Gaucher disease type I.
The open-label Phase I/II trial’s (NCT04145037) status was updated from recruiting to terminated on ClinicalTrials.gov on 23 August, and GlobalData evaluated the asset the next day. According to the study’s ClinicalTrials.gov listing, the trial was voluntarily terminated due to a business decision not to proceed, and not due to any safety or efficacy issue.
The multinational study evaluated the safety and efficacy of AVR-RD-02 in seven adult participants with a confirmed diagnosis of type I Gaucher disease. The study comprised five study periods which included screening, baseline, pre-gene therapy infusion, gene therapy infusion, and post-gene therapy infusion follow-up.
In the post-gene therapy infusion follow-up period, which lasted approximately 52 weeks, safety and efficacy assessments were performed to assess measures of safety, engraftment, and clinical response after the gene therapy infusion. The trial’s multiple co-primary endpoints measured the asset’s safety and efficacy.
AVR-RD-02 is a glucosylceramidase activator, which was developed using a four-plasmid lentiviral vector system called LV2 vector technology. The therapeutic candidate comprises autologous CD34+- enriched haematopoietic stem cells that are genetically modified with a lentiviral vector to encode and express a glucosylceramidase (GCase) specific gene. The drug candidate acts by enhancing the synthesis of the glucosylceramidase to increase the clearance of glucocerebroside, which ameliorates the disease condition.
Phase II oncology trial termination
Alphamab Oncology’s KN046 saw its PTSR fall in thymic carcinoma after the termination of an investigator-led Phase II trial. The PTSR dropped by seven points to 16%.
The Phase II trial’s (NCT04925947) status on ClinicalTrials.gov was updated from recruiting to terminated [Data collected did not support the study endpoints] on 25 August, and GlobalData appraised the asset on 28 August.
The Phase II study evaluated the efficacy and safety of KN046 in patients with advanced thymic carcinoma who progressed after previous immune checkpoint inhibitor treatment.
The trial measured the drug’s anti-tumour activity using the subject disease response rate as defined by the RECIST 1.1 criteria until the study’s completion, as the primary endpoint. While the study was anticipated to recruit 29 subjects, it ended with four. The trial was sponsored by Cornell University’s Weill Medical College.
KN046 is a recombinant humanized PD-L1/CTLA-4 bispecific antibody.
Boehringer’s Phase I/II trial completion
Boehringer Ingelheim’s BI-765128 saw its PTSR increase in diabetic retinopathy after the completion of a Phase I/II trial. The drug’s PTSR grew by nine points to 42%.
The status of the Phase I/II trial (NCT04919499) was updated from active, not recruiting to completed on ClinicalTrials.gov on 21 August, and GlobalData evaluated the asset on the same day.
The primary purpose of the trial was to study the safety and tolerability of single rising intravitreal doses in patients with diabetic macular ischemia who have received laser treatment. The trial enrolled 46 patients.
BI-765128 has an undisclosed mechanism of action. The Ingelheim am Rhein, Germany-based company is developing the drug candidate for the treatment of diabetic retinopathy.
Phase I trial completion in splenic marginal zone B cell lymphoma
Hutchison MediPharma’s amdizalisib saw its PTSR increase in splenic marginal zone B cell lymphoma after the completion of a Phase I trial. The drug’s PTSR grew by six points to 75%.
The status of the Phase I trial (NCT03128164) was updated from active, not recruiting to completed on ClinicalTrials.gov on 23 August, and GlobalData evaluated the asset on the following day. The primary purpose of the trial was to assess the safety, pharmacokinetics, and preliminary efficacy of amdizalisib in patients with lymphoma.
The trial enrolled 200 patients, while only 83 were originally anticipated to participate. Amdizalisib selectively inhibits Phosphatidylinositol 3-Kinase (PI3K) delta.
The Pudong, Shanghai-based company is developing the drug candidate for the treatment of hematological B cell malignancies including chronic lymphocytic leukaemia (CLL), indolent non-Hodgkin lymphoma, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), marginal zone B cell lymphoma (MZL), Waldenstrom macroglobulinaemia (WM), peripheral T-cell lymphomas (PTCL) and mantle cell lymphoma (MCL).
Read the last edition:Pipeline Moves: Advancement prospects halt for refractory acute myeloid leukaemia therapy after trial suspension
Need to know:
GlobalData’s proprietary model uses a combination of machine learning and an algorithm to calculate an individual drug’s PTSR and LoA. While LoA provides the probability of a drug ultimately receiving market authorization, PTSR indicates the probability of a drug’s advancement to the next stage of clinical development. The model uses datapoints from individual drugs, clinical trials, regulatory milestones, company, and financial databases.