In this week’s edition of Pipeline Moves, we look at Merck KGaA’s berzosertib in small-cell lung cancer and solid tumours, as well as Amgen ’s AMG 330 (eluvixtamab) in myelodysplastic syndrome. We also review Exelixis ’s Cabometyx (cabozantinib) in cervical cancer and AbViro in Dengue fever.

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Berzosertib’s advancement chances drops

Merck KGaA’s oncology asset berzosertib saw a decrease in its Phase Transition Success Rate (PTSR) in small-cell lung cancer and solid tumours after a Phase II trial was discontinued due to the low probability of the study meeting its pre-defined objective. In the trial’s main portion, the primary endpoint is objective response from first administration up to 15 months. 

The PTSR decreased by 28 points to 25% in small-cell lung cancer and 27 points to 7% in solid tumours. GlobalData evaluated the asset on June 8 after a press release was issued on June 3. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The open-label, single-arm study (NCT04768296) anticipated to enrol 86 participants with relapsed, platinum-resistant small-cell lung cancer. The trial looked into berzosertib in combination with the chemotherapy topotecan. Berzosertib inhibits ATR kinase activity.

The study has a safety run-in portion with primary endpoints looking at dose-limiting toxicities, treatment-emergent adverse events, and other safety parameters.  The media release states the combination’s safety was consistent to what was observed previously in other studies. The Phase II trial lists EDM Serono as the sponsor, which is Merck KGaA’s healthcare business.

Amgen terminates myelodysplastic syndrome study

Amgen’s eluvixtamab saw its PTSR reduce by 25 points to 36% in myelodysplastic syndrome after a Phase I study was terminated. Amgen terminated the trial due to a prioritisation decision. The PTSR change took effect on June 3 after a ClinicalTrials.gov update on June 2.

The multi-site trial (NCT02520427) was anticipated to enrol 256 participants but recruited only 96 subjects with myeloid malignancies. The study was set to evaluate the safety of eluvixtamab given as continuous intravenous infusion, and to determine the maximum tolerated dose and/or a biologically active dose. Eluvixtamab is a bi-specific T-cell engager (BiTE) antibody that targets CD33 and CD3 epsilon antigens.

Cabometyx cervical cancer trial terminated

Exelixis’s Cabometyx saw its PTSR slump in cervical cancer after a Phase II trial sponsored by University of South Alabama was terminated due to the primary investigator leaving the institution. The PTSR decreased by 10 points to 26%. GlobalData evaluated the asset on June 8 after a ClinicalTrials.gov update on June 7.

The open-label study (NCT04230954) anticipated to enrol 39 participants with recurrent, persistent and/or metastatic cervical cancer with PD-L1 tumour positivity. Nine patients were eventually recruited.  

The trial was designed to evaluate the efficacy and safety of Cabometyx in combination with Merck’s Keytruda (pembrolizumab). Cabozantinib is approved for hepatocellular carcinoma, metastatic renal cell carcinoma, renal cell carcinoma, and thyroid cancer.

Dengue fever trial completes

AbViro’s AV-1 human monoclonal antibody saw its PTSR increase by seven points reaching 43% in Dengue fever following a Phase I study completion. The trial’s status was marked as completed on ClinicalTrials.gov on June 03, with GlobalData evaluating the asset on June 06.

The first-in-human Phase I study (NCT04273217) investigated the safety of AV-1 in 42 healthy adult participants. The primary outcomes of the study measured the number of participants with physical and clinical exam abnormalities, incidence and severity of adverse events, among others.

Dengue fever is an infectious viral disease with no available therapy options apart from supportive care. The disease is spread by mosquitos and affects approximately 390 million people annually. 2 billion people are at risk for infection globally, making Dengue a public health concern.

On May 20, Clinical Trials Arena reported on the surge of Dengue fever cases and how manufacturers have struggled to develop antivirals and vaccines due to poorly coordinated clinical research and information gaps on how the virus evolves.  

Need to Know:

GlobalData’s proprietary model uses a combination of machine learning and an algorithm to calculate an individual drug’s PTSR. PTSR indicates the probability of a drug’s advancement to the next stage of clinical development. The model uses data points from the individual drugs, clinical trials, regulatory milestones, company, and financial databases.