“2 in 1” immunotherapy in advanced kidney cancer
Villejuif, 7th June 2022
MEDI5752A is a new bispecific monoclonal antibody with two distinct targets, thus representing a “two in one” immunotherapeutic agent. This medication was assessed for the first time in man in a phase I study using a range of doses in patients with solid tumours and then in a group of patients with advanced stage kidney cancer. The results show that in terms of side effects, this 2 in 1 immunotherapy seems to be equivalent to a combination of two immunotherapeutic agents. Otherwise, the preliminary findings suggest a promising response rate as a first-line treatment. The responses in patients who had not previously received immunotherapy seemed to be marked and prolonged. This study was presented at an oral session of the American Society of Clinical Oncology (ASCO) on the 5th of June by Dr Laurence Albiges, Head of the Department of Oncological Medicine at Gustave Roussy.
Abstract No. 107 presented orally by Dr Laurence Albiges Sunday 5th June 2022 at 5.33 pm
MEDI5752 is a new bispecific antibody with a novel mechanism of action. This results from the fact that it is a single molecule capable of inhibiting two known distinct immunotherapeutic target sites, PD1 and CTLA-4. “A combination of these two antibodies has shown improved survival in kidney cancer and this therapeutic combination is already available in France (nivolumab and ipilimumab). But we did not previously have a single drug with dual targeting,” explained Dr Albiges, Head of the Department of Oncological Medicine at Gustave Roussy and lead investigator on the study.
Reduction of tumour load in one patient in two
This first bispecific antibody was administered for the first time in man (first-in-human) in a phase I study. This study initially explored a variety of dose levels (dose escalation) before employing the agent on a larger scale in two expansion cohorts comprising kidney and lung cancer patients.
Dr Albiges presented the first results for the kidney cancer cohort at the ASCO meeting. 78 patients with metastatic disease who had never received any treatment or who were on second-line treatment were divided between the different dose levels: 500, 750 and 1500 mg. MEDI5752 was administered in hospital as an infusion at 3-weekly intervals.
The first study criterion concerned assessment of side effects. The main toxic effects reported (cutaneous, hepatic and thyroid-related) were not unexpected and were seen particularly with the highest dose levels. The 750 mg dose seemed to be associated with a reduction of risk of occurrence of these side effects.
The results also showed that the patients who had never previously received treatment responded best to this dual immunotherapy in a single medication. Some 58.3% of them showed a reduction of tumour load at a median follow-up of 18 months. “Responses were early, marked and prolonged with no real dose effect; the 750 and 1500 mg levels seemed to be fairly similar in effect,” noted Dr Albiges.
This novel promising strategy of dual immunotherapy in a single agent ought to result in an increased immune response and to lead to new combined therapies.
Further studies are awaited to define the best dose for patients with advanced renal cancer.
Abstract No. 107
Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 bispecific checkpoint inhibitor, as monotherapy in patients (pts) with advanced renal cell carcinoma (RCC): Preliminary results from an FTIH trial.
Clinical Science Symposium
Sunday 5th June 2022 | 17:33 – 17:45 UTC+2