Data presented at ASCO showed patients treated with a single, priming dose of tremelimumab plus IMFINZI achieved longest median survival among regimens tested
WILMINGTON, DE, USA I May 29, 2020 I Results from the global Phase II Study 22 trial testing AstraZeneca’s tremelimumab, an anti-CTLA4 antibody and potential new medicine, added to IMFINZI® (durvalumab) demonstrated promising clinical activity and tolerability in patients with advanced hepatocellular carcinoma (HCC). HCC is the most common type of liver cancer.1
In the primary endpoint of the trial evaluating safety, all experimental arms demonstrated an acceptable profile and no new safety signals were identified. Patients treated with a single, priming dose of tremelimumab 300mg added to durvalumab every four weeks (T300+D regimen) achieved a median overall survival (OS) of 18.7 months in a key secondary endpoint. The OS result for the T300+D regimen was the longest among treatments tested in the trial, which included IMFINZI monotherapy, tremelimumab monotherapy and two regimens of the two combined.
In other key secondary endpoints, objective response rate (ORR) confirmed by independent central review was 24% with the T300+D regimen, and median duration of response (DoR) was not yet reached at the time of data cut-off. A unique T-cell profile for patients in the T300+D arm was associated with treatment response, suggesting complementary biological activity.
R. Kate Kelley, MD, Associate Professor of Clinical Medicine, Department of Medicine, University of California San Francisco and principal investigator said, “In Study 22, we were able to induce a stronger immune response and enhance the clinical activity of IMFINZI in patients with advanced liver cancer by combining with a single dose of tremelimumab, a novel approach designed to prime the immune response using CTLA-4 inhibition at the start of therapy. These exciting results suggest that dual checkpoint blockade with tremelimumab and IMFINZI may have a role in a challenging cancer where patients have few treatment options.”
José Baselga, Executive Vice President, Oncology R&D, said, “Based on these compelling results, we see the potential for a single, priming dose of tremelimumab plus IMFINZI to change the treatment landscape and improve outcomes for patients with advanced liver cancer, a setting where new treatments are urgently needed. The Study 22 data are also an encouraging sign for our Phase III HIMALAYA trial testing this regimen in liver cancer, with data expected later this year.”
Summary of Results
| Study 22 Safety and Efficacy | ||||||||
| T300i+Dii | Dii | Ti | T75i+Dii | |||||
| Dosing | T300i mg x 1 dose + D1500ii mg Q4W | D1500ii mg Q4W | T750i mg Q4W x 7 doses, Q12W thereafter | T75i mg x 4 doses + D1500ii mg Q4W | ||||
| Median Total Treatment Duration, months (min.-max.) | 3.7 (0.8-27.1) | 3.7 (0.7-34.3) | 3.7 (0.9-31.2) | 2.4 (0.6-31.4) | ||||
| Safety | ||||||||
|
T300i+Dii (n=74) |
Dii (n=101) |
Ti (n=69) |
T75i+Dii (n=82) |
|||||
| Grade 3/4 trAEsiii, n (%) | 26 (35.1) | 20 (19.8) | 30 (43.5) | 20 (24.4) | ||||
| Serious trAEsiii, n (%) | 12 (16.2) | 11 (10.9) | 17 (24.6) | 12 (14.6) | ||||
| Grade 5 trAEsiii, n (%) | 1 (1.4) | 3 (3.0) | 0 | 1 (1.2) | ||||
| Discontinuation due to trAEsiii, n (%) | 8 (10.8) | 8 (7.9) | 9 (13.0) | 5 (6.1) | ||||
| Efficacy | ||||||||
|
T300i+Dii (n=75) |
Dii (n=104) |
Ti (n=69) |
T75i+Dii (n=84) |
|||||
| Median OS, months (95% CI) | 18.73 (10.78-27.27) | 13.57 (8.74-17.64) | 15.11 (11.33-20.50) | 11.30 (8.38-14.95) | ||||
| ORR, % (95% CI) | 24.0 (14.9-35.3) | 10.6 (5.4-18.1) | 7.2 (2.4-16.1) | 9.5 (4.2-17.9) | ||||
| Median DoR, months | NRiv | 11.17 | 23.95 | 13.21 | ||||
- Tremelimumab
- Durvalumab
- Treatment-related adverse events
- Not reached
Results evaluating safety and efficacy from parts two and three of the Phase II Study 22 trial were presented during the 2020 American Society of Clinical Oncology ASCO20 Virtual Scientific Program on Friday, May 29, 2020.
IMFINZI is not currently approved to treat HCC in any country, alone or in combination with tremelimumab. In January 2020, IMFINZI and tremelimumab were granted Orphan Drug Designation in the US for the treatment of HCC.
Indications
IMFINZI is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who:
- Have disease progression during or following platinum-containing chemotherapy.
- Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.
IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
Please see complete Prescribing Information, including Medication Guide.
NOTES TO EDITORS
About Study 22
Study 22 is an open-label, multicenter, global, four-part Phase II trial evaluating the safety and efficacy of several treatments in 433 patients with advanced HCC in the 1st- or 2nd-line setting. The first part of the trial evaluated the safety of the tremelimumab plus IMFINZI combination. Parts two and three are evaluating IMFINZI monotherapy, tremelimumab monotherapy, and tremelimumab plus IMFINZI combination therapy, and part four evaluates bevacizumab plus IMFINZI combination therapy. Results presented are for 332 patients in parts two and three, who were evaluated for safety and efficacy with a data cut-off of 28 February 2020. The trial is being conducted in 45 centers across 9 countries, including in the US, Europe, and Asia. Primary endpoints include number of patients reporting adverse events and serious adverse events, and number of patients experiencing dose-limiting toxicities. Secondary endpoints include overall survival, objective response rate, and duration of response.
About Liver Cancer
Liver cancer is the fifth leading cause of cancer death in the US, with approximately 20% of patients alive five years after diagnosis.2,3 HCC represents about 75-80% of all primary liver cancers.1,4 Between 80-90% of all patients with HCC also have chronic liver disease, which is primarily caused by infection with the hepatitis B or C viruses.5,6 Chronic liver disease is associated with inflammation that, over time, results in immunosuppression and can lead to the development of HCC.7,8 The unique immune environment of liver cancer provides clear rationale for researching medicines that harness the power of the immune system to treat HCC.9 A critical unmet need exists for patients with HCC who face limited treatment options. More than half of patients are diagnosed at advanced stages of the disease, often when symptoms first appear.10,11
About HIMALAYA
HIMALAYA is a randomized, open-label, multicenter, global Phase III trial of IMFINZI monotherapy and the T300+D regimen including a single, priming dose of tremelimumab 300mg added to IMFINZI every four weeks versus the standard-of-care medicine sorafenib, a multi-kinase inhibitor, in 1,324 patients with unresectable, advanced HCC who have not been treated with prior systemic therapy and are not eligible for locoregional therapy (treatment localized to the liver and surrounding tissue). The trial is being conducted in 189 centers across 16 countries, including in the US, Canada, Europe, South America and Asia. The primary endpoint is overall survival and key secondary endpoints include objective response rate and progression-free survival. HIMALAYA is the first Phase III trial to test dual immune checkpoint blockade in the 1st-line advanced HCC setting.
About IMFINZI® (durvalumab)
IMFINZI is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
IMFINZI is approved in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. IMFINZIis approved for the 1st-line treatment of extensive-stage small cell lung cancer (ES-SCLC) in combination with SoC chemotherapy in the US and Singapore. IMFINZI is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.
As part of a broad development program, IMFINZI is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumors.
About Tremelimumab
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation, priming the immune response to cancer and fostering cancer cell death. Tremelimumab is being tested in a clinical trial programme in combination with IMFINZI® (durvalumab) in NSCLC, SCLC, bladder cancer, head and neck cancer and liver cancer.
About AstraZeneca Support Programs
AstraZeneca strives to ensure that appropriate patients and their oncologists have access to IMFINZI and relevant support resources. These include educational resources, an Oncology Nurse Educator program and affordability and reimbursement programs, such as Access 360™.
Additionally, AstraZeneca has launched Lighthouse, a program that provides support to patients during any immune-mediated adverse events they may encounter during treatment, through medically trained Lighthouse Advocates. The program aims to make patients’ treatment experience as comfortable as possible. Find out more about Lighthouse at LighthouseProgram.com or call 1-855-LHOUSE1(1-855-546-8731).
About AstraZeneca’s Approach to Immuno-Oncology (IO)
Immuno-oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumors. The Company’s IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumor immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumor types.
The Company is pursuing a comprehensive clinical trial program that includes IMFINZI as a monotherapy and in combination with tremelimumab in multiple tumor types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca’s Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumors.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
References
- ASCO. Liver Cancer: Introduction. Available at https://www.cancer.net/cancer-types/liver-cancer/introduction. Accessed May 2020.
- National Cancer Institute. Cancer Stat Facts: Common Cancer Sites. Available at: https://seer.cancer.gov/statfacts/html/common.html. Accessed May 2020
- National Cancer Institute. Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. Available at: https://seer.cancer.gov/statfacts/html/livibd.html. Accessed May 2020.
- ASCO. ASCO Answers Liver Cancer. Available at: https://seer.cancer.gov/statfacts/html/common.html. Accessed May 2020.
- Dos Santos P, et al. Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus: a retrospective cohort study. World J Gastroenterol. 2018 February 7; 24(5): 613-622. DOI: 10.3748/wjg.v24.i5.613.
- Hiotis SP, et al. Hepatitis B vs. hepatitis C infection on viral hepatitis-associated hepatocellular carcinoma. BMC Gastroenterol 12, 64 (2012) doi:10.1186/1471-230X-12-64.
- Makarova-Rusher OV, et al. The yin and yang of evasion and immune activation in HCC. J Hepatol. 2015; 62 (6): 1420-1429.
- Del Campo JA., et al. Role of inflammatory response in liver diseases: Therapeutic strategies. World journal of hepatology. 2018; 10(1), 1–7. doi:10.4254/wjh.v10.i1.1.
- Han Y, et al. Human CD141CTLA-41Regulatory Dendritic Cells Suppress T-Cell Response by Cytotoxic T-LymphocyteAntigen-4-Dependent IL-10 and Indoleamine-2,3-Dioxygenase Production in Hepatocellular Carcinoma. Hepatology. 2014 Feb; 59 (2): 567-79.
- Colagrande S, et al. Challenges of advanced hepatocellular carcinoma. World J Gastroenterol. 2016;22(34):7645–7659 doi:10.3748/wjg.v22.i34.7645.
- ACS. Can Liver Cancer Be Found Early? Available at: https://www.cancer.org/cancer/liver-cancer/detection-diagnosis-staging/detection.html. Accessed May 2020.
SOURCE: AstraZeneca
