Sanofi drops lung cancer ADC tusamitamab ravtansine
French drugmaker Sanofi has halted the development of its antibody-drug conjugate (ADC) tusamitamab ravtansine after the drug failed a phase 3 trial in non-small cell lung cancer (NSCLC).
The drug, which targets carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) on tumour cells, was unable to improve progression-free survival in the CARMEN-LC03 trial in previously treated patients with CEACAM5-positive non-squamous NSCLC compared to docetaxel chemotherapy.
The decision to abandon the study and further development of tusamitamab ravtansine came on the advice of the trial’s independent data monitoring committee and despite a trend towards improved overall survival (OS) with the ADC.
Trial participants will have the option to stay on their current therapy if they are seeing a benefit, determined by their healthcare provider, or to transition to an appropriate standard-of-care therapy.
“Although the results are not what we hoped for, our research and work to advance potentially transformative therapies in areas of high unmet need for people living with cancer will not stop,” said Sanofi’s chief medical officer Dietmar Berger.
“We will continue to explore the potential of CEACAM5 as a biomarker in cancer types where it is highly expressed,” he added.
Sanofi also said it would continue to look at medicines based on tusamitamab, the CEACAM5-directed antibody component of the ADC, which was previously known as SAR408701.
It had been working towards regulatory filings in the US and Europe this year, so the demise of the programme knocks a hole in its late-stage pipeline and undermines Sanofi’s stated ambition to build its presence in oncology.
The development comes after Sanofi abandoned the development of oral selective oestrogen receptor degrader (SERD) amcenestrant for breast cancer last year after another phase 3 miss. Now, the group's only mid- to late-stage cancer programmes include efforts to extend the indications of blood cancer therapy Sarclisa (isatuximab) and phase 2 anti-ICOS antibody alomfilimab for solid tumours.
In addition to the CARMEN-LC03 study, Sanofi was also testing tusamitamab ravtansine in phase 2 trials in combination with other drugs – including MSD’s PD-1 inhibitor Keytruda (pembrolizumab) and Eli Lilly’s anti-VEGF drug Cyramza (ramucirumab) – in advanced solid tumours.
The pharma group licensed ex-China rights to tusamitamab ravtansine from Chinese biotech Innovent in 2017, and expanded the agreement last year to include Chinese rights to the ADC as well as a pegylated formulation of interleukin-2 codenamed SAR444245.
