USFDA grants priority review to Roche’s glofitamab

The United States Food and Drug Administration (USFDA) has accepted Roche’s Biologics Licence Application (BLA), and granted priority review for glofitamab, an investigational CD20xCD3 T-cell engaging bi-specific antibody, for the treatment of adult patients with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) after two or more lines of systemic therapy, a statement from Roche notified.

The statement also said that the FDA is expected to make a decision on approval of this novel cancer immunotherapy by 1st July, 2023. If approved, glofitamab would be the first fixed-duration, off-the-shelf CD20xCD3 T-cell engaging bi-specific antibody available to treat people with an aggressive lymphoma who have previously received multiple courses of treatment.

The BLA is based on positive data from the pivotal phase-I/II NP30179 study, which included patients who had previously received multiple courses of therapy, with 85.1 per cent of patients refractory to their most recent therapy and about one-third (33.1 per cent) having received prior CAR T-cell therapy. Results showed that 40 per cent of patients (n=62/155) achieved a Complete Response (CR; a disappearance of all signs of cancer), and 51.6 per cent (n=80/155) achieved an Objective Response (OR; the combination of CR and partial response, a decrease in the amount of cancer in their body). The median follow-up time was 13.4 months. Among those who achieved a CR, 73.1 per cent continued to experience a response at 12 months, while the median duration of CR was not reached. The median duration of response was 18.4 months, according to the statement.

Further, the statement mentioned that an earlier cut-off of data from the phase-I/II study showed that glofitamab, given as a fixed-duration treatment, resulted in early and durable complete remissions. In this analysis, presented at the 64th American Society of Hematology 2022 Annual Meeting and simultaneously published in the New England Journal of Medicine in December 2022, most patients who had achieved a CR at the end of treatment experienced durable responses. The median CR follow-up from the end of treatment was 11.5 months (95 per cent confidence interval [CI]: 10.5-16.4). Twelve months after the end of treatment with glofitamab, 61 per cent of patients (n=37/61) maintained a CR, 92.6 per cent remained progression-free and only one patient (n=1/44) experienced disease progression, according to the statement.

The most common adverse event was Cytokine Release Syndrome (CRS), which was generally low grade (48.1 per cent of patients had grade one and 12.3 per cent had grade two). Most CRS events were associated with initial administration of glofitamab (in cycle 1). The incidence of grade three or higher CRS was 3.9 per cent, with no grade five events. Only one patient (n=1/155) discontinued glofitamab due to CRS, the statement added.

The FDA will review the glofitamab BLA under the granted Fast Track Designation. Data from the phase-I/II NP30179 study of glofitamab were submitted for review to the European Medicines Agency (EMA), and submissions to additional health authorities worldwide are ongoing, the statement stated.

It also noted that glofitamab is part of Roche’s industry-leading CD20xCD3 T-cell engaging bi-specific antibody clinical programme, which is the broadest and most advanced in lymphoma. A robust clinical development programme for glofitamab is ongoing, including the phase-III Starglo trial, evaluating glofitamab in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with second line plus Diffuse Large B-Cell Lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Additional studies are ongoing to investigate the molecule as a monotherapy and in combination with other medicines for the treatment of patients with B-cell NHLs, including DLBCL, mantle cell lymphoma and other blood cancers.