Merck-Kelun lung cancer drug cut risk of tumour progression by 65 per cent, ASCO data show
A new antibody-drug conjugate (ADC) class result in lung cancer treatment emerged in the abstract Merck and its Chinese partner Kelun Biotech released ahead of the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Sacituzumab tirumotecan (SAC-TMT) cut the risk of tumour progression in advanced non-small cell lung cancer (NSCLC) by 65 per cent versus standard care.
The Phase III TROPION-LUNG02 trial enrolled 614 patients; all had previously received platinum-based chemotherapy and immune checkpoint inhibitor therapy. Patients were randomised 1:1 into two arms: SAC-TMT versus physician's choice of chemotherapy (docetaxel or pemetrexed). The primary endpoint was progression-free survival. The SAC-TMT arm hit a median 9.2 months, the control arm 3.4 months — a 65 per cent risk reduction.
Overall survival, the secondary endpoint, has not yet matured, but interim analysis at 18.7 months showed a 57 per cent survival rate in the SAC-TMT arm versus 39 per cent in the control arm. Safety profile: Grade 3 or higher haematological toxicity was 42 per cent in the SAC-TMT arm and 38 per cent in the control. Interstitial lung disease occurred in 8 per cent of SAC-TMT patients, with five deaths (0.8 per cent) — a known safety signal for the ADC class.
The TROP2-targeted ADC mechanism: SAC-TMT carries an antibody that binds to the TROP2 antigen, which is overexpressed on lung cancer cells; the antibody is internalised by the cancer cell and releases its payload, the topoisomerase-1 inhibitor tirumotecan. This results in limited off-target damage in healthy cells and high cytotoxicity in cancer cells. Currently the only approved TROP2-targeted ADC is Gilead's Trodelvy, in breast cancer.
Merck's ASCO representative Dr Eliav Barr told the press briefing: "This result is the first Phase III positive read-out for the ADC class in lung cancer. We have demonstrated the class is workable in lung." Barr added that Merck would submit approval applications to the FDA and European Medicines Agency (EMA) in the third quarter. Kelun Biotech's spokesperson said the company would file its own NMPA application in China in the first quarter of 2027.
Kelun Biotech's discovery team established the TROP2-targeted ADC platform in 2018 at the Chengdu laboratory in Sichuan. SAC-TMT first entered clinical development for breast cancer; the lung cancer programme launched in 2022. Merck signed a licensing deal in March 2023 worth USD 1.4 billion upfront and up to USD 8 billion across three ADC molecules.
Goldman Sachs healthcare analyst Sarah Lewis's note placed SAC-TMT's annual lung cancer market potential at USD 4 to 7 billion. "This is the first major product reshaping Merck's post-Keytruda transition pipeline," Lewis wrote. Keytruda's main patent runs out in September 2028; four of the 12 important Phase III trials in Merck's pipeline involve TROP2-targeted ADCs.
There is an important access dimension for developing countries. SAC-TMT will launch in the US with an estimated annual price tag of USD 280,000 (Merck's highest-priced analytic reference). Türkiye's social security pricing commission is expected to start negotiations. Kelun Biotech is targeting an annual price of USD 12,000-15,000 in China, with reimbursement discussions opened with the National Healthcare Security Administration. Brazil's ANVISA and India's CDSCO timelines are scheduled for early 2027.
The past two years of ADC class development signal an important change is approaching in lung cancer treatment protocols. Daiichi-AstraZeneca's HER2-targeted ADC Enhertu received FDA approval for lung cancer in December 2024 but is limited to 3-4 per cent of NSCLC patients. SAC-TMT's TROP2 target covers close to 50 per cent of the population — a much broader market.
Dr Roy Herbst, director of the lung cancer programme at Yale Cancer Center, told STAT News: "This kind of progression-free survival improvement in second-line treatment is at a level we have not seen in the last decade. If overall survival is also positive, the protocol change will move in parallel with the conventional approval process." Herbst predicted NCCN guidelines would be updated within six months.
The Phase III TROPION-LUNG02 data will be presented in detail at the ASCO meeting on Monday; Merck shares closed Friday up 4.2 per cent. A meaningful frame of hope for patients and physicians is beginning to take shape on the approval path of the ADC class for lung cancer.
For decisions about cancer treatment, please consult a qualified oncologist; this article does not substitute for medical advice.