Roche already dominates the anti-CD20 space and, if data at Ash this weekend are anything to go by, has a good chance of continuing to do so. The pharma giant’s bispecific mosunetuzumab generated durable responses in an impressive proportion of very poor prognosis non-Hodgkin lymphoma patients, some of whom had relapsed after Car-T therapy.
The toxicity profile also looks manageable, with cytokine release syndrome seen but not at levels likely to derail the project. Roche has long argued that the relatively simple bispecific approach, compared with cell therapies, is the way forward in many tumour types. These results help make that case.
The data are from a large phase I/IIb study, called GO29781, evaluating mosunetuzumab on its own or in combination with Tecentriq, in patients with relapsed or refractory NHL or chronic lymphocytic leukaemia. The results are being formally presented at Ash’s plenary session tomorrow, but were detailed in a press conference at the haematological cancer meeting on Saturday morning.
The data are from the monotherapy cohort, and concern 270 poor prognosis NHL patients with a median five lines of prior systemic therapies. Most had failed to respond to a previous anti-CD20 approach, while 22 were refractory to a Car-T therapy.
Dr Stephen Schuster of the University of Pennsylvania will detail responses in aggressive as well as indolent NHL, with complete responses coming in at 19.4% and 43.3% respectively. Durability also looks compelling, particularly in the indolent subset, with 24 of the 29 complete response patients remaining in remission up to 26 months after coming off treatment.
Responses in those patients who relapsed after Car-T therapy are particularly eyecatching, though the numbers are small for now. Data from 18 subjects were presented: mosunetuzumab generated seven responses, four of which were complete.
Most patients will have nowhere to go after Car-T so this is an encouraging finding; at the same time it suggests that bispecifics could find a place in earlier lines of therapy.
The fact that mosunetuzumab looks like it is being positioned as a threat to Car-T is especially interesting in light of Dr Schuster’s involvement in the development of Novartis’s Kymriah. It was Dr Schuster who led that Car-T therapy’s pivotal lymphoma study, Juliet (ICML – Novartis’s non-infusion mystery centres on Juliet’s design, June 14, 2017).
Dr Schuster told the press conference that he had used mosunetuzumab as a bridge to Car-T, and that in patients with very fast moving disease an off-the-shelf option is necessary, given the treatment delays with Car-T.
"The future for this drug, and this off-the-shelf approach to exploiting cellular therapy, is the direction that we will be pursing in the future," he said.
He also pointed out that, unlike Car-T therapies, patients can be re-treated with mosunetuzumab. The GO29781 trial design dictated that treatment was discontinued after eight cycles of mosunetuzumab if a complete response was achieved, and retreatment was allowed if these patients subsequently relapsed. Of four patients who were retreated, only three responded, though one of these was a complete remission.
This patient remains in complete response 13 months after retreatment; their initial complete response was durable for 16 months.
The final touch here is safety: Dr Schuster described the risks as "definitely acceptable, vis-a-vis Car-T." 29% of patients had cytokine release syndrome, though most events were grade 1-2. Neurological adverse events were seen in 44% of patients, but again were largely low grade, mostly headache.
These results add to a growing body of evidence to suggest that bispecifics will challenge Car-T therapies in certain settings. And in this area Roche is looking very well placed; the company also has an earlier stage anti-CD20 bispecific project, RG6026, that some believe is looking even stronger.