Boehringer advances duo for aggressive cancers into phase 3
Boehringer Ingelheim is stepping up its push into oncology with new clinical trials for the pathfinder product Hernexeos and experimental drug obrixtamig in hard-to-treat cancers.
Last year's approval of Hernexeos (zongertinib) as the first oral, targeted therapy for previously treated patients with HER2-mutant advanced non-small cell lung cancer (NSCLC) marked the return of Boehringer to the oncology category, and the company has now launched a new trial – Beamion-LUNG-3 – to try to move it onto earlier stages of the disease.
Hernexeos was granted accelerated approval by the FDA for previously-treated HER2-mutated NSCLC based on Beamion-LUNG-1, and had its label extended in February to include first-line treatment, becoming the first targeted therapy as an initial treatment option for patients with this type of cancer on the back of the Beamion-LUNG-2 data.
With the third trial in the programme, Boehringer has set its sights on positioning Hernexeos as adjuvant monotherapy – compared with physician's choice standard of care - in stage 2-3B HER2-mutant NSCLC patients who have undergone complete surgical resection and have received either neoadjuvant or adjuvant therapy.
It has been projected that Hernexeos could generate over $1 billion in peak global sales for Boehringer as a treatment for HER2-mutant NSCLC alone, with upside potential if it can be developed for other solid tumours that feature HER2 alterations.
Obrixtamig aiming to challenge Amgen's Imdelltra
Arguably with even greater commercial potential – perhaps $1 to $2 billion at peak, according to some analysts – DLL3/CD3 T-cell engager obrixtamig (BI 764532) will move into phase 3 for small cell lung cancer (SCLC) in the DAREON-Lung-1 study and extrapulmonary neuroendocrine carcinoma (epNEC) in DAREON-NEC-1.
Boehringer is hoping to position obrixtamig as a competitor to Amgen's bispecific T-cell engager (BiTE) Imdelltra/Imdylltra (tarlatamab), which has been approved in Europe and the US as a second-line treatment option for extensive-stage SCLC after first-line, platinum-based chemotherapy. Amgen's drug made $627 million in global sales last year.
The German pharma group is running the two trials to see if adding obrixtamig to standard care will improve outcomes in biomarker-informed patient SCLC and epNEC populations.
DLL3 is a protein that is found in a majority of SCLC tumours, potentially up to 96%, but is rarely found in healthy cells. It is also commonly seen in EpNEC, which Boehringer said is a historically under-researched cancer for which survival outcomes have not improved in decades.
"With the launch of these trials, we are advancing our precision oncology ambitions to move targeted therapies into earlier treatment lines and bring biomarker-informed science into late-stage development," said Lykke Hinsch Gylvin, Boehringer's chief medical officer.
"By focusing on the biology of each tumour, we aim to give patients facing cancer more precise treatment options with the goal of improving outcomes where the need is greatest," she added.
Obrixtamig is one of three drug candidates that have emerged from Boehringer's longstanding alliance with the UK's Oxford BioTherapeutics, a specialist in developing antibody-based therapeutics, with a fourth due to enter the clinic later this year.
Boehringer is also running trials of BI 765049, an investigational B7-H6-targeting T-cell engager, in colorectal cancer, and recently started human testing of BI 3820768, which has few publicly available details and, for now, no disclosed target.
You can learn more about Boehringer's plans for Hernexeos and its wider oncology strategy in pharmaphorum editor in chief Jonah Comstock's interview with the drugmaker's global head of oncology, Itziar Canamasas, at this year's ASCO congress.
