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August 30, 2022

Pipeline Moves: Sanofi terminates breast cancer trial, approval prospects plummet

The Clinical Trials Arena team also investigates trial terminations in idiopathic thrombocytopenic purpura, soft tissue sarcoma, and solid tumours.

By Clinical Trials Arena Team

This week on Pipeline Moves, we bring news of four trial terminations, starting with Sanofi’s Phase III study in HER-2 positive breast cancer. We follow that up with a trial termination from UCB in idiopathic thrombocytopenic purpura (ITP), and two investigator-sponsored study terminations in soft tissue sarcoma and solid tumors.

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Sanofi terminates Phase III breast cancer study

Sanofi’s amcenestrant (SAR439859) saw its Likelihood of Approval (LoA) drop by 28 points to 17% in Human Epidermal Growth Factor Receptor 2 (HER-2) positive breast cancer, after the termination of the Phase III AMEERA-6 trial. The AMEERA-6 study was focused on hormone receptor positive (HR+) breast cancer patients and allowed those with a Her2+ status as long as they had completed adjuvant anti-Her2 treatment and chemotherapy.

The AMEERA-6 study (NCT05128773) was terminated after Sanofi decided to discontinue amcenestrant’s global clinical development program, as per a 17 August  company press release. The program discontinuation was based on an interim analysis of the Phase III AMEERA-5 trial (NCT04478266), which compared amcenestrant in combination with Pfizer’s Ibrance (palbociclib) and with Novartis’s Femara (letrozole) in combination with Ibrance in patients with estrogen receptor-positive (ER+)/ Her-2 negative advanced breast cancer. While there were no safety concerns, data from the interim analysis showed that the amcenestrant/Ibrance combination did not meet the prespecified efficacy boundary and an independent data monitoring committee recommended the termination of the trial.

The Phase III AMEERA-6 trial evaluated the safety and efficacy of amcenestrant compared with AstraZeneca’s (LON:AZN) Nolvadex (tamoxifen) in adult patients with HR-positive early breast cancer who stopped adjuvant aromatase inhibitor (AI) therapy due to toxicity related to treatment.  Amcenestrant is an oral selective estrogen receptor degrader (SERD) that prevents estrogen binding, thereby inhibiting estrogen-dependent cancer cell proliferation. All studies with amcenestrant will be discontinued and participants will be transitioned to Femara in combination with Ibrance or other appropriate therapies.

UCB terminates blood disorder Phase III trial

UCB’s rozanolixizumab saw its LoA in ITP plummet 34 points to 31% following a Phase III trial termination. ClinicalTrials.gov updated the study’s status from “Recruiting” to “Terminated” on 19 August , and the LoA change took effect on 22 August .

The Phase III study (NCT04200456) was terminated due to a “strategic business decision” and not due to safety concerns, as per the trial listing. The trial had an enrollment target of 93 patients with persistent or chronic primary ITP, but only 33 patients enrolled prior to the termination.

ITP is a blood disorder characterised by abnormally low levels of platelets in the blood. The primary endpoint of the Phase III study was durable platelet response during at least eight of the final 12 weeks of treatment.

Rozanolixizumab is a monoclonal antibody that blocks the interaction between the neonatal FC receptor (FcRn) and IgG receptor, thereby regulating immune cell response. The mAb is also in development for myasthenia gravis, autoimmune encephalitis, and chronic inflammatory demyelinating polyneuropathy.

Investigator-led soft tissue sarcoma study terminates

Amgen’s Imlygic (talimogene laherparepvec) saw its Phase Transition Success Rate (PTSR) drop in soft tissue sarcoma after an investigator-led Phase Ib/II trial was suspended. The reason behind the suspension was listed as ‘evaluating trial design’ on the study’s ClinicalTrials.gov entry. The PTSR declined by 10 points to 26%. GlobalData evaluated the asset on 22 August  after a ClinicalTrials.gov update on 19 August .

The open-label, single-arm trial (NCT04599062) was anticipated to enroll 46 participants with locally advanced soft tissue sarcomas. The study intended to investigate the safety and relative efficacy of Imlygic in combination with external beam radiation therapy (EBRT).

Imlygic is an antineoplastic agent that causes tumour lysis and releases tumour-derived antigens. The oncolytic viral therapy was approved for treating metastatic melanoma in 2015.

Investigator-led solid tumour trial terminates

VasGene Therapeutics’ Ephrin Type B Receptor 4 (EphB4-HSA) recombinant albumin fusion protein (Vas-01) saw its PTSR drop in three oncology indications after an investigator-led Phase I trial in unspecified adult solid tumours was terminated. The reason for termination was listed as “lack of funding” on the study’s ClinicalTrials.gov listing. The trial’s status was updated on ClinicalTrials.gov on 24 August , with GlobalData evaluating the asset on the next day. The study was sponsored by the University of Southern California and the principal investigator was Dr Anthony El-Khoueiry.

The PTSR decreased by 26 points in hepatocellular carcinoma and malignant pleural mesothelioma, settling at 28% for both indications. The PTSR also declined by 25 points to 26% in colorectal cancer.

The investigator-led, first-in-human Phase I study (NCT01642342) evaluated the safety and efficacy of EphB4-HSA in 102 adult patients with pathologically-proven advanced solid tumours that have been unresponsive to previous standard treatment. One of the study’s primary endpoints measured treatment-related toxicity and adverse events at different drug doses for at least four weeks following treatment. The study’s other coprimary endpoints measured the number of patients with complete or partial response, and stable or progressive disease, as well as time to failure and survival for a period of up to two years.

EphB4-HSA is a recombinant fusion protein that inhibits EphB4. It interferes with the binding of Ephrin B2 (Efnb2), EphB4 and Ephrin Type A Receptor 3 (EphA3) to their native receptors and reduces the proliferation of Efnb2 and/or EphB4 over-expressing tumour cells.

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.

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