This week on Pipeline Moves, we kick off by looking at the termination of a Phase II investigator-led trial of Eli Lilly’s merestinib in solid tumours.
Meanwhile, RevImmune terminated a Phase II trial of its Mycobacterium avium infection candidate CYT-107 and a Phase II investigator-led trial of Leap Therapeutics sirexatamab was terminated.
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On a positive note, Trellis Bioscience completed a Phase I trial of calpurbatug (TRL1068) in gram-positive and gram-negative bacterial infections.
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Eli Lilly’s merestinib has seen its Phase Transition Success Rate (PTSR) drop after an investigator-led Phase II trial of the candidate in solid tumours was terminated.
The PTSR for merestinib dropped in solid tumors by 15 points to 11%. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The status of the trial which was being run by Dana-Farber Cancer Institute was changed from active, not recruiting to terminated on ClinicalTrials.gov on 11 April. GlobalData evaluated the asset on 12 April. The ClinicalTrials.gov listing says the trial was terminated after funding was pulled.
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By GlobalDataThe Phase II trial (NCT02920996) was an open-label study that investigated merestinib in non-small cell lung cancers harbouring MET exon 14 mutations and solid tumours with NTRK rearrangements. The ClinicalTrials.gov listing states that the trial enrolled 12 patients, with eight being removed from the study due to adverse events. The reasons listed for the other four patients ceasing involvement in the trial included death, missing (subjects), subject noncompliance and physician decision.
Merestinib is an inhibitor of the proto-oncogene c-Met, also known as hepatocyte growth factor receptor [HGFR]. The drug binds to c-Met, to inhibit phosphorylation and disrupt signal transduction pathways.
Phase II trial of Mycobacterium avium infection candidate terminated
France-based RevImmune’s CYT-107 has seen its PTSR drop by more than half after a Phase II trial of the candidate in Mycobacterium avium infection was terminated. The PTSR for CYT-107 dropped in Mycobacterium avium infection by 17 points to 15%.
The status of the trial was changed from recruiting to terminated on ClinicalTrials.gov on 9 April. GlobalData evaluated the asset on 12 April. The ClinicalTrials.gov listing says the termination was due to non-convincing results.
The Phase II trial (NCT04154826) was a single-centre, single-blinded study involving patients with refractory nontuberculous mycobacteria lung disease to ascertain the pharmacokinetics, safety, efficacy, and tolerability of two dose levels of CYT-107. RevImmune anticipated to enrol 12 patients but terminated the study after enrolling eight.
CYT-107 acts as an IL-7 agonist. IL-7 stimulates the production of significant numbers of T-cells, both CD4 and CD8, so they produce anti-tumor-specific responses.
Phase II bile duct cancer trial terminated
Leap Therapeutics’s sirexatamab saw its PTSR decline following the termination of an investigator-led Phase II trial in bile duct cancer (cholangiocarcinoma), gallbladder cancer, and metastatic biliary tract cancer.
The drug’s PTSR decreased by 11 points to 34% in bile duct cancer, 10 points to 35% in gallbladder cancer, and 15 points to 13% in metastatic biliary tract cancer. The study was sponsored by Massachusetts General Hospital.
The trial’s status was updated on its ClinicalTrials.gov from ongoing, not recruiting to terminated on 10 April and GlobalData evaluated the asset on 12 April. The study was terminated after the study did not meet response criteria to move on to stage two according to the trial’s ClinicalTrials.gov listing.
The Phase II trial (NCT04057365) evaluated the combination of sirexatamab and Bristol Myers Squibb’s Opdivo (nivolumab) in previously treated patients with advanced biliary tract cancer.
Sirexatamab acts by inhibiting dickkopf-1 (Dkk-1). The monoclonal antibody (mAb) is under development for the treatment of various cancers.
HER2-negative breast cancer candidates’ chances drop after trial termination
Accutar Biotechnology’s AC-0682 saw its PTSR in human epidermal growth factor receptor 2 (HER2)-negative breast cancer drop 24 points to 37% after a Phase I study for locally advanced or metastatic ER+ breast cancer was terminated.
The Phase I trial’s (NCT05080842) status was updated from active, not recruiting to terminated on ClinicalTrials.gov. As per the listing, the trial was voluntarily terminated because the sponsor’s development strategy was adjusted.
The trial was terminated on 9 April, as per the trial registry, with GlobalData evaluating the product on 12 April.
The open label, single-group assignment study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of the treatment in patients with HER2-negative breast cancer. The objective of the study was to identify a safe, recommended dosage for AC-0682, which was done by using co-primary endpoints evaluating the incidence of dose-limiting toxicities (DLTs), and the incidence of treatment-emergent adverse events (TEAEs) and clinically significant laboratory abnormalities of Grade 3 or higher following treatment administration.
AC-0682 is an orally bioavailable, small molecule degrader of the transcription factor estrogen receptor (ER) alpha, which is a hormone-regulated protein that plays a critical part in the initiation and proliferation of breast cancer.
Gram-positive and gram-negative bacterial infection candidate trial completes
Trellis Bioscience’s calpurbatug (TRL1068) saw a six-point increase in its PTSR for gram-positive and gram-negative bacterial infections, landing at 58% in both indications.
The study’s (NCT04763759) Clinicaltrials.gov status changed from active, not recruiting to completed on 8 April, and the PTSR change was recorded on 12 April. The Phase I blinded, single ascending dose trial investigated the safety, pharmacokinetics, and activity of calpurbatug on subjects with prosthetic joint infection of the knee or hip, undergoing primary two-stage exchange arthroplasty. The trial explored the incidence of abnormal physical findings, abnormal serum chemistries and hematology, and other abnormalities as its primary endpoints. The Phase I study ended on 13 March.
Calpurbatug is an intravenous monoclonal antibody therapy that binds to a specific antigen in the biofilm. This causes the dissolution of the biofilm, thus treating the infection. The therapy was developed to treat gram-positive and gram-negative bacterial infections caused by prosthetic joints.
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.
