The combination of Imfinzi (durvalumab) and Imjudo (tremelimumab) has demonstrated unprecedented overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC), the most common type of liver cancer. The Phase III HIMALAYA trial revealed that approximately one in five patients treated with this combination survived for five years, a significant milestone in a disease with historically poor prognosis.
The HIMALAYA trial compared the combination of Imfinzi and Imjudo to sorafenib, a standard first-line treatment for advanced HCC. The results showed a statistically significant and clinically meaningful improvement in OS for the Imfinzi plus Imjudo arm. This outcome suggests a potential paradigm shift in the treatment landscape for advanced liver cancer, offering a new hope for long-term survival.
AstraZeneca's Commitment to GI Cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2022, GI cancers collectively represented approximately 4.9 million new cancer cases leading to approximately 3.3 million deaths. Within this program, the company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers.
In addition to its indications in BTC and HCC, Imfinzi is being assessed in combinations, including with Imjudo, in liver, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease across settings.
The Company is also assessing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, in combination with chemotherapy as an adjuvant therapy in BTC and as a 1st-line treatment in patients with HER2-negative, locally advanced unresectable or metastatic gastroesophageal junction cancers.
Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is approved in the US, China and several other countries for HER2-positive advanced gastric cancer and is being assessed in colorectal cancer. It also has been assessed in multiple GI settings including BTC in the DESTINY-PanTumor02 Phase II trial, and it was recently approved in the US for the treatment of unresectable or metastatic HER2-positive solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in the US, EU and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).
AstraZeneca is advancing multiple modalities that provide complementary mechanisms for targeting Claudin 18.2, a promising therapeutic target in gastric cancer. These include AZD0901, a potential first-in-class antibody drug conjugate licensed from KYM Biosciences Inc., currently in Phase III development; AZD5863, a novel Claudin 18.2/CD3 T-cell engager bispecific antibody licensed from Harbour Biomed in Phase I development; and AZD6422, an armoured autologous chimeric antigen receptor T cell (CAR-T) therapy, currently being evaluated in an Investigator Initiated Trial (IIT) in collaboration with AbelZeta in China.
In early development, AstraZeneca is developing two Glypican 3 (GPC3) armoured CAR-Ts in HCC. AZD5851, currently in Phase I development, is being developed globally, and C-CAR031 / AZD7003 is being co-developed with AbelZeta in China where it is under evaluation in an IIT.
Immuno-Oncology Approach
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
