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May 31, 2022

Pipeline Moves: Myelodysplastic syndrome study on partial hold, solid tumour trial terminated

We also take a look at the suspension of a Tecentriq combo trial, and a small-cell lung cancer study termination.

By Clinical Trials Arena Team

In this week’s edition of Pipeline Moves, the Clinical Trials Arena team reports on cancer clinical trials. First up is Foghorn Therapeutics’s myelodysplastic syndrome (MDS) asset, on its advancement prospects on the heels of a Phase I partial clinical hold. We also report on Bristol-Myers Squibb’s (BMS) termination of a Phase I trial in solid tumours.

In other news, an investigator-led Phase I/II trial studying Roche’s Tecentriq (atezolizumab) as a combo partner was suspended, leading to its advancement shot in bile duct and gallbladder cancers to decline. Ascentage Pharma terminated a Phase Ib/II trial, leading to small-cell lung cancer asset’s likelihood of moving forward in the pipeline to decrease.

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Foghorn clinical trial on hold after participant death

Foghorn’s FHD-286 saw its Phase Transition Success Rate (PTSR) nosedive 25 points to 27% in MDS after the FDA placed a Phase I trial on partial clinical hold. The pause is due to a trial participant death with potential differentiation syndrome.

Foghorn announced the partial hold in a May 19 press release, with the PTSR change taking effect on May 23. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The 50-patient Phase I trial (NCT04891757) is a dose-escalation study of FHD-286 in relapsed and/or refractory MDS and acute myelogenous leukemia (AML). Differentiation syndrome, associated with therapies targeting MDS and AML, is caused by the rapid release of cytokines. It has symptoms ranging from cough, trouble breathing, and low blood pressure, all the way to kidney failure and potentially death.

The FDA has requested a “review of the safety database, risk mitigation strategies, and a breakdown of clinical activity across dose levels,” according to the company release. FHD-286 is an oral, small-molecule inhibitor of BRG1 and BRM, which are proteins implicated in chromatin regulatory system.

BMS terminates Phase I cancer clinical trial

BMS’s BMS-986299 saw its PTSR dive 21 points to 19% in solid tumours. This is after the company terminated a Phase I study due a change in its business objectives. The clinical trial status update on ClinicalTrials.gov was on May 23, with GlobalData evaluating the asset on May 24.

The open-label Phase I (NCT03444753) investigated BMS-986299 as a monotherapy and as a part of the combination of BMS’s own Opdivo (nivolumab) and Yervoy (ipilimumab) in 82 participants with advanced solid tumours. The trial had multiple primary endpoints looking into adverse events and clinical laboratory abnormalities. BMS-986299 is designed to activate the NLRP3 receptor, with the intention to induce tumour cell death.

Tecentriq PTSR drops in bile duct, gallbladder cancer

Roche’s Tecentriq saw a decrease in its PTSR in bile duct cancer and gallbladder cancer after an investigator-led Phase I/II clinical trial was suspended. The suspension is due to pending protocol revision to lower the starting dose of Aveo Oncology’s Fotivda (tivozanib), Tecentriq’s combo partner in the trial. Hypertension was seen among study participants.

Tecentriq’s PTSR decreased by 11 points to 43% in bile duct cancer and 10 points to 45% in gallbladder cancer. GlobalData evaluated Tecentriq on May 25 after a ClinicalTrials.gov update on May 24.

The open-label, single-arm trial (NCT05000294) is designed to recruit 29 participants with immunologically cold tumours. University of Florida is listed as a clinicial trial sponsor, with Aveo and Roche subsidiary Genentech stated as collaborators. The study aimed to evaluate Tecentriq plus Fotivda in tumours which have a low response rate to checkpoint inhibitor alone.

Tecentriq is an anti-PD-L1 checkpoint inhibitor approved in transitional urothelial tract, non-small cell, and small-cell lung cancers, as well as in hepatocellular carcinoma and melanoma. Tyrosine kinase inhibitor Fotivda is approved in renal cell carcinoma.

Ascentage terminates Phase Ib/II trial

Ascentage’s APG-1252 (pelcitoclax) saw its PTSR drop by nine points to 14% in small-cell lung cancer after the company decided to terminate a Phase Ib/II clinical trial. The study’s terminated status was updated on ClinicalTrials.gov on May 19, with GlobalData appraising the asset on May 20.

The open-label Phase Ib/II clinical trial (NCT04210037) was designed to investigate APG-1252 plus chemotherapy paclitaxel in 28 patients with relapsed or refractory small-cell lung cancer. The Phase Ib portion had a primary endpoint looking into maximum tolerated dose with a 21-day timeframe, while the Phase II portion’s is partial or complete response measured within 12 months at start of therapy.

APG-1252 acts by inhibiting Bcl-2 and Bcl-xl proteins which regulate programmed cell death and apoptosis. Bcl-2 and Bcl-xl proteins are antiapoptotic molecules which are usually overexpressed in cancer cells.

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.

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