MHRA Grants Conditional Marketing Authorisation for Tepkinly[®]▼(epcoritamab) as a Bispecific Treatment for Adults with Relapsed or Refractory DLBCL After Two or More Lines of Systemic Therapy

TUE, OCT 24, 2023 11:55 CET

PRESS RELEASE - For UK consumer, medical and trade media only

• Diffuse large B-cell lymphoma (DLBCL) is an aggressive sub-type of non-Hodgkin’s lymphoma, with nearly 5,500 new diagnoses in the UK each year¹

• Bispecific antibodies represent a new class of therapies that work by introducing a local immune cell to a cancer cell, enabling the immune cell to attack and destroy the cancer²
   
• As the first and only subcutaneous bispecific injection, epcoritamab could offer eligible patients an additional treatment option³

MAIDENHEAD, UK, [23 October 2023] – AbbVie (NYSE: ABBV) today announced that the UK Medicines and Healthcare products Regulatory Agency has granted conditional Marketing Authorisation for Tepkinly^®▼ (epcoritamab) as a monotherapy for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), after two or more systemic therapies⁴. The conditional Marketing Authorisation for Great Britain is based on the single-arm Phase 1/2 EPCORE NHL-1 trial data, which demonstrated a 62% (86/139) overall response rate and 39% (54/139) complete response rate in patients. However, further data are awaited from an ongoing phase 3 confirmatory study^4,5,6.

Epcoritamab is the first and only licensed subcutaneous bispecific treatment option for adult patients with R/R DLBCL after two or more lines of systemic therapy, in Great Britain⁴. In contrast to some existing therapeutic options, epcoritamab does not require cell collection and engineering^4,5,7. The treatment is administered to eligible patients by clinicians as a weekly subcutaneous injection for 12 weeks, then moves to every other week for 24 weeks (12 injections), before continuing as one injection every 4 weeks until treatment is discontinued, either due to cancer progression or side effects⁴. Eligible patients are able to start epcoritamab therapy after appropriate pre-medication has been administered and monitoring for adverse events is available^4,5. Patients stay in hospital for 24 hours after the first full dose to monitor for side effects^4,5.

DLBCL is the most common sub-type of non-Hodgkin’s lymphoma (NHL), an aggressive blood cancer that develops in the lymphatic system, causing B-cell lymphocytes, a type of white blood cell, to grow abnormally¹. There are nearly 5,500 new DLBCL diagnoses each year in the UK¹. For the approximately 700 people in the UK with R/R DLBCL who have already received two or more treatments and require further therapy, prognosis is poor⁸. There are few treatments available for this patient population, and these are typically administered intravenously, via a needle or tube inserted into a vein⁹.

“Despite recent therapeutic advances, treatment options for patients with R/R DLBCL after two previous therapies are limited. For such patients living with this type of aggressive blood cancer, many experience disease progression and have poor prognosis”, said Professor Chris Fox, Professor of Haematology, School of Medicine, University of Nottingham and Honorary Consultant Haematologist, Nottingham University Hospitals NHS Trust. “As a novel bispecific antibody, given as a subcutaneous injection, epcoritamab offers a new treatment option for this difficult-to-treat patient group.”

Bispecific antibodies represent a new class of therapies that use the body’s immune system to kill cancer cells². Epcoritamab is a bispecific antibody designed to simultaneously bind to two proteins, cluster of differentiation (CD)3 on T cells in the immune system and CD20 on cancerous B cells (a type of white blood cell), in order to induce T-cell mediated killing of cancerous B cells². By targeting two cells, epcoritamab brings the immune T cell together with the cancerous B cell and activates the T cell to destroy the B cell². Epcoritamab must be delivered under the supervision of a healthcare professional qualified in the use of anti-cancer therapies with access to appropriate medical support to manage potential serious side effects, such as cytokine release syndrome (CRS) events^4,5.

Common serious adverse reactions observed in the single-arm Phase 1/2 EPCORE NHL-1 trial included CRS events, pneumonia, upper respiratory tract infections, febrile neutropenia, immune effector cell-associated neurotoxicity syndrome (ICANS) and pyrexia^4,5.

The conditional Marketing Authorisation is based on data from the single-arm Phase 1/2 EPCORE NHL-1 trial investigating epcoritamab as monotherapy for 139 patients with R/R DLBCL after two or more lines of systemic therapy^4,5. In the Phase 1/2 NHL-1 clinical trial, the overall response rate was 62% (n=86/139), meaning 62% of participants’ blood cancer went down by half or they had no cancerous cells remaining in their body (partial response or complete response)¹⁰. The complete response rate was 39% (n=54/139), meaning there is no evidence of disease from tests and scans in 39% of these hard-to-treat patients, who on average had already been through three types of treatment before starting the trial^10,11. The NHL-1 trial results demonstrate that epcoritamab prevented growth or spread of the cancer for an average of 15.6 months, and the patients lived for an average of 19.4 months from the start of epcoritamab therapy^4,5,10.

“AbbVie is committed to advancing care for people living with blood cancer. Today’s news is an important step forward in enabling us to provide this hard-to-treat patient group with an innovative subcutaneous treatment option”, said Belinda Byrne, Medical Director, AbbVie UK. “We are working with the NHS and relevant authorities to bring access to eligible patients and clinicians throughout the UK as quickly as possible.”

-Ends-

UK media contact:
Rachael Pink
AbbVie UK
T: +44 (0)7816 180 570
E: rachael.pink@abbvie.com

NOTES TO EDITORS:

Glossary

B cells / B lymphocytes: A type of white blood cell (an immune cell) that fights infection by producing antibodies¹². This is the blood cell that becomes cancerous in DLBCL¹.
Complete response rate of 39% (n=54/139)¹⁰: The total number of people in the trial who experienced the disappearance of all evidence of lymphoma in the body from tests and scans after treatment¹⁴.
Conditional Marketing Authorisation: The conditional Marketing Authorisation is based on data from the single-arm Phase 1/2 EPCORE NHL-1 trial investigating epcoritamab as monotherapy for 139 patients with R/R DLBCL after two or more lines of systemic therapy^3,9. The Medicines and Healthcare products Regulatory Agency may grant a conditional Marketing Authorisation where a medicinal product fulfils an unmet medical need and where comprehensive clinical data is not yet complete, but it is judged that such data will become available soon.
Median duration of response of 15.6 months⁴: The average length of time that a tumour continues to respond to treatment without the cancer growing or spreading¹³.
Median overall survival of 19.4 months¹⁰: The average time patients live for from the time they start treatment with epcoritamab¹³.
Overall response rate of 62% (n=86/139)¹⁰: The total number of people in the trial whose cancer has either gone away (a complete response) or shrunk (a partial response)¹⁴.
Refractory: Lymphoma that does not respond well to the first choice of treatment, and patient does not go into remission¹.
Relapse: Lymphoma that comes back after successful treatment and a period of remission¹.
Remission: When there is no evidence of lymphoma in the body from tests and scans after treatment, and no symptoms¹.
T cells / T lymphocytes: A type of white blood cell (immune cells) that help to protect us from viruses and cancers by attacking them directly¹².

About DLBCL
Lymphoma is a blood cancer that causes tumours to form in the lymphatic system¹. Lymphoma is divided into two main types called Hodgkin’s lymphoma and NHL¹⁵. DLBCL is a type of NHL and makes up almost 30% of all cases of NHL globally¹⁶. There are approximately 5,500 new cases of DLBCL in the UK each year¹. Patients with DLBCL typically have swollen lymph nodes in the neck, armpit or groin¹.

About TEPKINLY^® (epcoritamab)
Epcoritamab has been granted conditional Marketing Authorisation as a subcutaneous injection to treat adults in Great Britain with DLBCL that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received two or more treatments for their cancer⁴. The treatment is administered to eligible patients by clinicians as a weekly subcutaneous injection for 12 weeks, then moves to every other week for 24 weeks (12 injections) before continuing as one injection every 4 weeks until treatment is discontinued, either due to cancer progression or side effects⁴. 

Epcoritamab is an immunoglobulin G1-bispecific antibody created using Genmab’s proprietary DuoBody^® technology². Genmab’s DuoBody^®-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types². Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell mediated killing of CD20+ cells². CD20 is expressed on B cells and is a clinically validated therapeutic target in many B-cell malignancies, including DLBCL^17,18. Epcoritamab was designed specifically for high-specificity binding².

About the EPCORE™ NHL-1 clinical trial^3,4,19
EPCORE™ NHL-1 is a single-arm, open-label, multicentre safety and preliminary efficacy trial of epcoritamab that includes a Phase 1 first-in-human dose escalation part; a Phase 2a expansion part; and a dose optimisation part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell NHL, including DLBCL. Data from the dose escalation part of the study, which determined the recommended Phase 2 dose, were published in September 2021. In the Phase 2 expansion part, additional patients were treated with epcoritamab to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of R/R B-cell NHLs who had limited therapeutic options.

The primary endpoint of the Phase 2 expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy and rate of minimal residual disease negativity. The most common adverse reactions of any grade (≥20%) observed in the trial were CRS (50.9%), fatigue (30.5%), neutropenia (30.5%), injection-site reactions (29.9%), pyrexia (23.4%), abdominal pain (23.4%), nausea (21.6%) and diarrhoea (21.0%). The most common Grade 3–4 adverse reactions (≥2%) were neutropenia (23.4%), anaemia (10.2%), thrombocytopenia (7.2%), pneumonia (6.0%), fatigue (3.0%), CRS (3.0%), febrile neutropenia (2.4%), oedema (2.4%) and hypophosphataemia (2.4%). The most common serious adverse reactions (≥2%) were CRS (31.1%), pneumonia (7.2%), upper respiratory tract infections (2.4%), febrile neutropenia (2.4%), ICANS (2.4%) and pyrexia (2.4%). Four patients (2.4%) experienced a fatal adverse reaction (ICANS in one patient [0.6%] and pneumonia in three patients [1.8%]).

Results from the Phase 2 expansion part of the study were published in December 2022. More information can be found at https://classic.clinicaltrials.gov/ct2/show/NCT03625037.

About AbbVie in oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world’s most widespread and debilitating cancers. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines.

About AbbVie
AbbVie’s mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people’s lives across several key therapeutic areas – immunology, oncology, neuroscience and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at abbvie.co.uk. Follow @abbvieuk on X, formally known as Twitter, and YouTube

References

1. Lymphoma Action. Diffuse large B-cell lymphoma. Available from: https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/diffuse-large-b-cell-lymphoma [Last accessed: October 2023].
2. Engelberts PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52:102625.
3. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023;41(12):2238–2247.
4. Tepkinly GB. Summary of product characteristics.
5. Tepkinly. Summary of product characteristics. Available from: https://www.ema.europa.eu/en/documents/product-information/tepkinly-epar-product-information_en.pdf [Last accessed: October 2023].
6. ClinicalTrials.gov. A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/​R DLBCL (EPCORE DLBCL-1). Available from: https://clinicaltrials.gov/study/NCT04628494 [Last accessed: October 2023].
7. Ngu H, Takiar R, Phillips T, et al. Revising the Treatment Pathways in Lymphoma: New Standards of Care—How Do We Choose? Am Soc Clin Oncol Educ Book. 2022;42:1–14.
8. National Institute for Health and Care Excellence. Resource impact report: Axicabtagene ciloleucel for treating diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma after 2 or more systemic therapies (TA872). Available from: https://www.nice.org.uk/guidance/ta872/resources/resource-impact-report-pdf-11381453821 [Last accessed: October 2023].
9. Blood Cancer UK. Diffuse large B-cell lymphoma (DLBCL) treatment and side effects. Available from: https://bloodcancer.org.uk/understanding-blood-cancer/lymphoma/diffuse-large-b-cell-lymphoma/dlbcl-treatment-side-effects/dlbcl-relapsed-and-refractory-treatment [Last accessed: October 2023].
10. Jurczak W, Ghesquieres H, Karimi Y, et al. P1118: Longer follow-up from the pivotal epcore nhl-1 trial reaffirms subcutaneous epcoritamab induces deep, durable complete remissions in patients with relapsed/refractory large b-cell lymphoma. Hemasphere. 2023;7(Suppl):e081065c.
11. Lymphoma Action. Remission. Available from: https://lymphoma-action.org.uk/about-lymphoma-treatment-lymphoma/remission#complete [Last accessed: October 2023].
12. Cano RLE, Lopera HDE. Introduction to T and B lymphocytes. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al, (eds). Autoimmunity: From Bench to Bedside [Internet]. Bogota (Colombia): El Rosario University Press; 2013;18(5).
13. Delgado A, Guddati AK. Clinical endpoints in oncology - a primer. Am J Cancer Res. 2021;11(4):1121–1131.
14. Cancer Research UK. What do Clinical trial results mean? Available from: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/clinical-trial-results/what-do-clinical-trial-results-mean-0 [Last accessed: October 2023].
15. Lymphoma Out Loud. Lymphoma Signs and Symptoms. Available from: https://lymphomaoutloud.org/signs-symptoms [Last accessed: October 2023].
16. Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842–858.
17. Rafiq S, Butchar JP, Cheney C, et al. Comparative Assessment of Clinically Utilized CD20-Directed Antibodies in Chronic Lymphocytic Leukemia Cells Reveals Divergent NK Cell, Monocyte, and Macrophage Properties. J Immunol. 2013;190(6):2702–2711.
18. Singh V, Gupta D, Almasan A. Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response. J Cancer Sci Ther. 2015;7(11):347–358.
19. ClinicalTrials.gov. First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma (EPCORE™ NHL-1). NCT03625037. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT03625037 [Last accessed: October 2023].

UK-ONCNHB-230005 | October 2023