Fixed-Duration Glofitamab Approved in Europe for Relapsed/Refractory DLBCL

The European Commission has granted conditional marketing authorization to glofitamab (Columvi) for fixed-duration administration in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following 2 or more lines of systemic treatment.¹

The regulatory decision is based on findings from a cohort of the phase 1/2 NP30179 trial (NCT03075696) in which fixed-dose treatment with the bispecific antibody induced a complete response (CR) rate of 35.2%, and an overall response rate (ORR) of 50% in this population (n = 108). In those who had a CR with glofitamab, 74.6% (95% CI, 59.19%-89.93%) continued to respond at 1 year. The median time to first CR was 42 days (95% CI, 41-47), and the median duration of CR was not yet reached.

In this cohort, cytokine release syndrome (CRS) represented the most common toxicity experienced with glofitamab, occurring in 64.3% of patients, followed by neutropenia (37.7%), anemia (30.5%), and thrombocytopenia (24.7%). Notably, CRS events were largely low grade, with 48.1% and 12.3% of patients experiencing grade 1 and grade 2 CRS, respectively. CRS led to discontinuation of the bispecific antibody in 1 patient.

“As the lead investigator for the NP30179 study, I have seen firsthand the early and long-lasting responses that [glofitamab] can induce, when given to patients for a fixed period of time,” Michael Dickinson, MD, PhD, principal study investigator and associate professor at Peter MacCallum Cancer Centre and Royal Melbourne Hospital in Australia, stated in a press release. “It is exciting that with this approval, patients in Europe with heavily pretreated or refractory DLBCL will now have a new, potentially practice-changing treatment option that will allow them time off of therapy to resume their routine activities, helping to alleviate some of the physical and emotional burdens caused by cancer treatment.”

The early-phase trial enrolled patients with histologically confirmed DLBCL, transformed follicular lymphoma, high-grade B-cell lymphoma, or primary mediastinal large B-cell lymphoma (LBCL) whose disease relapsed after or was refractory to at least 2 prior lines of treatment, including at least 1 anti-CD20 antibody–based regimen and at least 1 anthracycline-based regimen.² Patients were also required to be at least 18 years of age and have an ECOG performance status of 0 or 1.

Patients were pretreated with obinutuzumab (Gazyva) at 1000 mg a week before their first dose of glofitamab. The bispecific antibody was then given as step-up doses of 2.5 mg on day 8 and 10 mg on day 15 of the first cycle of treatment; for cycles 2 through 12, the agent was given at 30 mg. Patients received treatment for the full 12 cycles or until they experienced disease progression or unacceptable toxicity.

CR by independent review committee (IRC) assessment served as the primary end point of the research. Secondary end points included ORR, duration of response, duration of CR, time to first CR, and time to first objective response; these end points were all examined by IRC and investigator assessment. Other end points of interest included CR by investigator assessment, progression-free survival, and overall survival.

Additional findings from a larger cohort of patients with heavily pretreated or refractory DLBCL (n = 155) indicated that the bispecific antibody induced a 39.4% (95% CI, 32%-48%) CR rate by IRC assessment, with a median DOR of 18.4 months (95% CI, 13.7-not reached). Moreover, the median time to first CR in this group was 42 days (95% CI, 42-44), with most of the first responses occurring approximately 1.4 months after glofitamab was initiated. The ORR achieved with the drug was 51.6% (95% CI, 43%-60%).

Regarding safety in this group, grade 1 CRC was reported in 47.4% of patients and grade 2 CRS was reported in 11.7% of patients. CRS was reported at the time of the initial doses of the bispecific antibody. Glofitamab-related toxicities led to treatment discontinuation in 3.2% of patients.

In June 2023, the FDA granted accelerated approval to glofitamab-gxbm (Columvi) for use in adult patients with relapsed or refractory DLBCL not otherwise specified or LBCL arising from follicular lymphoma, after at least 2 prior lines of systemic therapy.³ The decision was supported on data from NP30179.

References

1. European Commission approves Roche’s fixed-duration Columvi (glofitamab) for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. July 11, 2023. Accessed July 11, 2023. https://www.roche.com/media/releases/med-cor-2023-07-11
2. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231. doi:10.1056/NEJMoa2206913
3. FDA approves Genentech’s Columvi, the first and only bispecific antibody with a fixed-duration treatment for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Genentech. June 15, 2023. Accessed July 11, 2023. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs