On 21st February 2017, Ahmed Sawas, from Columbia University Medical Center, New York, and colleagues published in the British Journal of Haematology the results of an open-label, multicenter, phase I/II trial into the use of ublituximab in CLL or B-Cell NHL patients relapsed or refractory to rituximab therapy.
The phase I component of this study aimed to define the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT), and safety of ublituximab in this population. The phase II component aimed to determine the ORR, with secondary aims being safety, DoR, TTR, and PFS. Rituximab-refractory patients were defined as having progression within six months of rituximab treatment, with progression after six months of treatment end being classed as relapsed.
- Recruited = 35 pts, 2 pts discontinued due to AE, 1 pt SAE, and 1 pt withdrew consent, still evaluated for safety, 31 pts evaluable for efficacy
- Phase I = 20pts (8pts CLL, 7pts FL, 3pts MZL, 2pts MCL)
- Treatment: Fibonacci 3 + 3 dose-escalation of 450mg, 600mg, 900mg, 1200mg ublituximab
- CLL: Ublituximab on D1, D8, D15, of Cycle 1 and 2 (28 day cycles)
- NHL: Ublituximab on D1, D8, D15, D22 of Cycle 1, no dose in Cycle 2
- All pts then received ublituximab maintenance D1 of Cycles 3–5, then once every three months, for up to two years
- No DLT observed, therefore MTD was not identified
- 900mg chosen as recommended phase II dose due to no difference in ORR vs 1200mg, but with lower hematological toxicities
- Phase II = 15pts (5pts FL, 5pts MZL, 3pts MCL, 2pts DLBCL)
- Efficacy results phase I+II (31pts):
- ORR = 45% (NHL = 44%, CLL = 50%)
- FL ORR = 42%, MZL ORR = 71%, DLBCL ORR = 100%, CLL ORR = 50%
- CR = 13%, (FL = 17%, MZL = 29%)
- PR = 32% (CLL = 50%, FL = 25%, MZL = 43%, DLBCL = 100%)
- SD = 45%, PD = 10%
- Median TTR = 1.8 months
- Median DoR = 9.2 months
- Median PFS = 7.7 months (95% CI, 4.5–16.2)
- Median PFS rituximab-refractory pts = 4.7 months (95% CI, 1.9–16.2)
- ORR = 45% (NHL = 44%, CLL = 50%)
- All pts experience at least 1 AE
- ≥1 Grade 3/4 AE in 49% pts, SAE in 37% pts
- IRR = 40% pts,
- No febrile neutropenia reported
- No deaths due to treatment
In conclusion, the authors state that ublituximab treatment was shown to be well tolerated and effective in treating CLL and NHL patients who have failed rituximab therapy. Further studies are ongoing using ublituximab in combination with other agents such as lenalidomide (NCT01744912) and ibrutinib (NCT02006485).
- Sawas A. et al. A phase 1/2 trial of ublituximab, a novel anti-CD20 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma or chronic lymphocytic leukaemia previously exposed to rituximab. British Journal of Haematology. 2017 Feb 21. DOI: 1111/bjh.14534. [Epub ahead of print: 2017 Feb 21].
This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti-tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti-CD20 monoclonal antibody, in rituximab-relapsed or -refractory patients with B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukaemia (CLL). Induction therapy (doses of 450-1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL. Patients received ublituximab maintenance monthly during cycles 3-5, then once every 3 months for up to 2 years. Enrolled patients with B-NHL (n = 27) and CLL (n = 8) had a median of 3 prior therapies. No dose-limiting toxicities or unexpected adverse events (AEs) occurred. The most common AEs were infusion-related reactions (40%; grade 3/4, 0%); fatigue (37%; grade 3/4, 3%); pyrexia (29%; grade 3/4, 0%); and diarrhoea (26%; grade 3/4, 0%). Common haematological AEs were neutropenia (14%; grade 3/4, 14%) and anaemia (11%; grade 3/4, 6%). The overall response rate for evaluable patients (n = 31) was 45% (13% complete responses, 32% partial responses). Median duration of response and progression-free survival were 9·2 months and 7·7 months, respectively. Ublituximab was well-tolerated and efficacious in a heterogeneous and highly rituximab-pre-treated patient population.