ASCO 2024: Rakuten's photoimmunotherapy and Keytruda effective in HNSCC

Rakuten Medical, a US-based biopharmaceutical company, has reported promising interim results from its Phase Ib/II clinical trial involving ASP-1929, a photoimmunotherapy treatment. ASP-1929 is an innovative antibody-dye conjugate that combines cetuximab, an epidermal growth factor receptor (EGFR) antagonist antibody, with a light-activated dye, IRDue 700DX. When illuminated with red light via a laser device, this conjugate induces a photochemical reaction, causing membrane damage in cancer cells and leading to their selective necrosis.

The ongoing clinical trial is evaluating the combination of ASP-1929 with Merck & Co.'s Keytruda (pembrolizumab) for treating patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). Following these encouraging interim results, Rakuten Medical plans to initiate a global Phase III clinical trial in the second half of this year. This upcoming trial will assess the combination therapy as a first-line treatment for recurrent HNSCC, with overall survival as the primary endpoint.

Data from the Phase Ib/II trial (NCT04305795) will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, scheduled to take place in Chicago from May 31 to June 4. The study involved 19 patients, 18 of whom received both ASP-1929 and Keytruda therapies. Notably, as of the data cut-off on August 31, 2023, the median overall survival and duration of response had not yet been reached. The therapy demonstrated an objective response rate (ORR) of 35.3%, with four complete responses and two partial responses. At the 24-month mark, the estimated survival rate stood at 52.4%.

ASP-1929, which received fast track designation from the US Food and Drug Administration (FDA) in 2018, has already been approved in Japan for treating unresectable locally advanced or recurrent head and neck cancer. The therapy's mechanism involves cetuximab, a drug marketed under the name Erbitux by Bristol Myers Squibb, which is traditionally used for late-stage HNSCC and metastatic colorectal cancer.

The trial did identify some serious adverse reactions, such as dysphagia (difficulty swallowing) and tongue oedema (swelling). While no fatal events were reported, two Grade 4 events—laryngeal oedema and tumour haemorrhage—were observed, attributable to the advanced stage of the disease in the affected patients.

In addition to the clinical advancements, Rakuten Medical has also secured $119 million in a Series E financing round this March. The funds are intended to support the development of their Alluminox drug discovery platform and to finance the Phase III trial of ASP-1929 as a monotherapy (NCT03769506). This open-label Phase III study aims to enrol approximately 275 participants with recurrent HNSCC who have undergone at least two prior lines of therapy.

Overall, Rakuten Medical's ASP-1929 represents a promising advancement in the treatment of recurrent and/or metastatic HNSCC. The positive interim data and subsequent plans for a global Phase III trial underscore the potential of this novel photoimmunotherapy to significantly impact patient outcomes. The forthcoming results from the ASCO Annual Meeting are highly anticipated and will provide further insights into the efficacy and safety of this combination therapy.