- Data for investigational CD20xCD3 bispecific antibodies and new combination regimens with Polivy showed enhanced clinical benefits for people with non-Hodgkin lymphoma in early studies
“People with difficult-to-treat blood cancers such as non-Hodgkin lymphoma still need more options to help improve outcomes,” said
While approximately 500,000 people worldwide are diagnosed with NHL each year, treatment options are currently limited and resistance to existing therapies or relapse following treatment is common.1 The most prevalent form of NHL, accounting for about 40% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma (DLBCL), that comes with a life expectancy of weeks or months if left untreated.2,3
In clinical trials to date, the investigational CD20xCD3 T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, have shown promising responses across multiple types of NHL, including relapsed or refractory (R/R) DLBCL and follicular lymphoma (FL). Pivotal data for these medicines are expected this year and
- Phase I NP30179 study investigating step-up dosing of glofitamab in heavily pre-treated R/R NHL, showed high, ongoing complete responses (CRs) and an acceptable safety profile. After a median follow-up of 6.3 months, results showed that glofitamab achieved a complete metabolic response rate, defined as the disappearance of metabolic tumour activity, of 71.4% in patients with aggressive (fast-growing) NHL. The most common adverse events (AEs) were cytokine release syndrome (CRS) (63.5%), neutropenia (38.5%), and pyrexia (32.7%); CRS events were mostly low grade and confined to the first cycle of treatment.4
- Phase I/II GO40516 study of mosunetuzumab in combination with Polivy in R/R NHL showed promising efficacy and an acceptable safety profile. The regimen achieved a CR of 54.5% in all patients. Eighty six percent of patients evaluated had aggressive NHL, and these patients achieved a CR rate of 47.4%. The most frequent treatment-related AEs were neutropenia (45.4%), fatigue, nausea, and diarrhoea (all 36.4%) and CRS (9.1%; all Grade 1).5
Broad development programmes are ongoing for mosunetuzumab and glofitamab, including the phase III GO42909 trial investigating mosunetuzumab plus lenalidomide versus MabThera®/Rituxan® (rituximab) plus lenalidomide in R/R FL, which will soon be enrolling patients. For glofitamab, the phase III GO41944 open-label, randomised trial designed to evaluate the safety and efficacy of glofitamab plus gemcitabine and oxaliplatin (glofit-GemOx) versus MabThera/Rituxan plus GemOx in patients with R/R DLBCL, is also ongoing.
- New triplet combination of Polivy with MabThera/Rituxan and lenalidomide, which demonstrated promising activity in difficult-to-treat R/R DLBCL, based on results from the phase Ib/II GO29834 study. With a median follow-up of 9.7 months, median overall survival was 10.9 months (95% CI: 7.4–NE) and median progression-free survival was 6.3 months (95% CI: 4.5–9.7) in patients treated with the triplet. The most commonly reported Grade 3-4 AEs were neutropenia (58.0%), thrombocytopenia (14.0%), infections (14.0%) and anaemia (11.0%).6
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About Roche’s investigational bispecifics in haematology
About Polivy® (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of NHL, making it a promising target for the development of new therapies.7,8 Polivy binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.9,10 Polivy is being developed by
About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single-agent and in combination with Gazyva®/Gazyvaro® (obinutuzumab), following pre-treatment with a one-time, fixed-dose of Gazyva/Gazyvaro, in people with relapsed or refractory (R/R) B-cell NHL. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose and tolerability.
About the GO40516 study
The GO40516 study [NCT03671018] is a phase I/II, multicentre, open-label study, evaluating the efficacy, safety, tolerability and pharmacokinetics of mosunetuzumab in combination with Polivy in people with B-cell NHL. It consists of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with R/R DLBCL and 2L+ R/R FL. Outcome measures include best overall response rate, maximum tolerated dose and tolerability.
About the GO29834 study
The GO29834 study [NCT02600897] is a phase Ib/II, multicentre, open-label study, evaluating the efficacy and safety of Polivy with MabThera® /Rituxan® (rituximab) and lenalidomide in R/R DLBCL. Outcome measures include complete response and tolerability.
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References
[1] GLOBOCAN 2020. World Fact Sheet. [Internet; cited
[2] Cancer.Net. Leukemia – Lymphoma –Non-Hodgkin:
[3] Zhou et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era (NCCN-IPI) Blood. 2014
[4]
[5] Budde E, et al. Promising tolerability and efficacy results from dose-escalation in an ongoing Phase Ib/II study of mosunetuzumab with polatuzumab vedotin in patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma. Poster presented at: ASCO Annual Meeting; 2021
[6] Diefenbach C, et al. Polatuzumab vedotin + rituximab + lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma: primary analysis of a Phase 1b/2 trial Poster presented at: ASCO Annual Meeting; 2021
[7] Dornan D, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 2009;114:2721-29.
[8] Pfeifer M, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015;29:1578-86.
[9] Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2010;21:5-13.
[10] ADC Review. What are antibody-drug conjugates? [Internet; cited
https://adcreview.com/adc-university/adcs-101/antibody-drug-conjugates-adcs/
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