Clinical Setback for Connect Biopharma Sends Shares Plunging Over 40%; Merck Acquires EyeBio for $3B; AstraZeneca/Daiichi Sankyo Launch Phase III Trial of Osimertinib + Dato-DXd in China

1. Alphamab Oncology's Bispecific Antibody Fails Again in Phase III Pancreatic Cancer Trial, Stock Plummets Over 40%

On the morning of May 29, the stock price of Alphamab Oncology-B in Hong Kong plummeted suddenly, with the maximum intraday drop reaching 58%. By the close, the decline was 44.75%, and the total market value shrank to HK$2.538 billion.

On the news front, on May 28, Alphamab Oncology announced that the overall survival (OS) results of the KN046-303 trial did not meet the pre-set statistical endpoint. This means that this clinical trial, which had repeatedly caused sharp declines in Alphamab Oncology's stock price, has officially been declared a failure.

KN046 is a bispecific antibody targeting PD-L1 and CTLA-4 developed by Alphamab Oncology, with independent intellectual property rights. The innovative design of KN046 includes: the fusion of single-domain antibodies against CTLA-4 and PD-L1 with different mechanisms; it can specifically accumulate in the tumor microenvironment with high PD-L1 expression and deplete Treg cells that suppress tumor immunity.

It is worth mentioning that KN046 is one of Alphamab Oncology's bispecific antibody products closest to commercialization. Currently, multiple registrational clinical trials for KN046 are underway, including first-line treatment combined with chemotherapy for squamous NSCLC and first-line treatment for pancreatic cancer in a pivotal phase III clinical trial. This time, it was the failure of the phase III clinical trial for first-line treatment of pancreatic cancer.

Prior to this, the stock price of Alphamab Oncology had plummeted multiple times due to new drug development falling short of expectations. In May last year, the phase 3 clinical trial ENREACH-LUNG-01 (KN046-301) for KN046 failed to achieve statistical significance in overall survival (OS), resulting in an unsuccessful unblinding, which directly led to a sharp drop in the stock price of Alphamab Oncology. In November last year, negative rumors resurfaced in the market, causing its stock price to plummet nearly 50% within two trading days.

2、$3 Billion! Merck Acquires EyeBio, Obtains a Tri-specific Antibody

3. Osimertinib + Dato-DXd! Daiichi Sankyo/AstraZeneca Initiate Phase III Clinical Trial in China for First-Line Treatment of EGFR-Mutated NSCLC

On May 27, according to the CDE Clinical Trial Registration and Information Disclosure Platform, Daiichi Sankyo/AstraZeneca registered and initiated a new Phase III clinical trial, TROPION-Lung14, for Dato-DXd (DS-1062a/Derdalumab), in combination with Osimertinib as a first-line treatment for EGFR mutation-positive locally advanced or metastatic NSCLC patients. (Registration Number: CTR20241813)

The primary endpoint is PFS assessed by BICR, with secondary endpoints including ORR, DOR, and OS, among others. Public data shows that this study had previously been registered and initiated on the ClinicalTrials.gov platform (Registration Number: NCT06350097). The part initiated this time is the China segment, planning to enroll 174 participants in China and 582 internationally, with the first participant already enrolled on May 10.

Previously, Dato-DXd has achieved positive results in later-line treatment of NSCLC patients with EGFR mutations. The TROPION-Lung05 study specifically targets patients with advanced or metastatic NSCLC who experienced disease progression during or after receiving at least one tyrosine kinase inhibitor and at least one platinum-based chemotherapy regimen (with or without other systemic therapies).

Data from the study presented at the 2023 ESMO Congress showed that, in patients with EGFR mutations (n=78, the most common genomic mutation), those treated with Dato-DXd had an ORR of 43.6%, a DCR of 82.1%, an mPFS of 5.8 months, and an mDOR of 7.0 months.