The game is on for TROP2 antibody-drug conjugates in first-line triple-negative breast cancer.
Less than a month after an approval for Daiichi Sankyo and AstraZeneca’s Datroway for front-line TNBC patients who are not candidates for PD-1/L1 inhibitors, the FDA has handed Gilead Sciences’ Trodelvy a rivaling approval that allows the drug to be used regardless of patients’ PD-L1 status.
The new FDA approval for Trodelvy in first-line TNBC now allows the first-in-class TROP2 ADC to be used either alone for patients who aren’t eligible for PD-1/L1 inhibitors or in combination with Merck & Co.’s Keytruda for those with PD-L1-positive tumors, defined as a combined positive score of at least 10.
In its extended market showdown with Datroway, Gilead boasts the advantage of familiarity, as its initial FDA go-ahead for 2020 was in previously treated TNBC. In a June 24 release, the California company highlighted that doctors have “well-established experience” with Trodelvy, which has treated more than 75,0000 breast cancer patients globally over the past six years.
Trodelvy’s latest approval is backed by findings from two phase 3 trials. In Ascent-03, Trodelvy significantly reduced the risk of progression or death by 38% versus chemotherapy in PD-(L)1 treatment-ineligible patients. And in Ascent-04, also known as Keynote-D19, Trodelvy and Keytruda improved progression-free survival (PFS) by 35% versus Keytruda and chemo in PD-L1-positive cancer.
At least for now, the PD-L1-positive component makes Trodelvy’s TNBC label broader. But AZ and Daiichi’s Tropion-Breast05 trial in that population aims to level the playing field, with a readout expected in 2027. However, the choice of Imfinzi as Datroway’s combination partner may be a weakness in that effort, as the AZ PD-L1 inhibitor is not approved in TNBC.
In the drugs’ shared PD-L1-negative use, Datroway boasts a unique overall survival (OS) benefit. In the phase 3 Tropion-Breast02 trial in patients with PD-(L)1-ineligible TNBC, Datroway significantly reduced the risk of death versus chemotherapy by 21% and improved PFS by 43%.
Trodelvy’s Ascent-03 trial was not yet able to claim an OS win at the time of primary PFS analysis. Gilead has flagged a high cross-over rate, which could affect the final OS results. Among control-arm patients who started subsequent treatment, 82% received Trodelvy. By comparison, in Datroway’s trial, among control patients who received any postprogression anticancer therapy, 41% got a subsequent ADC.
The situation was reversed in the two TROP2 ADCs’ initial battleground of previously treated HR-positive, HER2-negative breast cancer.
Trodelvy was approved there in 2023 based on the phase 3 TROPiCS-02 study showing it significantly improved OS by 21% and PFS by 34% versus chemo.
Datroway followed into a similar indication two years later. But despite a 37% PFS improvement, the Tropion-Breast01 trial showed no OS benefit for Datroway versus chemo at the final analysis. An imbalance in subsequent ADC use was observed, with 12.3% in the Datroway arm, versus 24% in the control group.
In addition to first-line TNBC, Datroway and Trodelvy are separately undergoing phase 3 tests as adjuvant treatments for high-risk, early-stage TNBC. The Ascent-05 and Tropion-Breast03 trials started around the same time in 2022 and could both read out next year.
While the two TROP2 ADCs duke it out in breast cancer, Datroway’s future in the broader oncology landscape could be further clarified this year with the much-anticipated readout of the Avanzar trial in first-line non-small cell lung cancer (NSCLC).
Mainly thanks to its approval in late-line EGFR-mutated lung cancer, Datroway’s sales reached $102 million in the first quarter globally.
As for Trodelvy, its market potential has been significantly narrowed after a series of phase 3 flops, including its most recent failure in first-line, PD-L1-high NSCLC. Besides adjuvant TNBC, the drug’s remaining phase 3 trials include those for extensive-stage small cell lung cancer and second-line endometrial cancer.
Meanwhile, a three-way TROP2 market battle has already taken shape in China with the addition of Kelun-Biotech’s sac-TMT, which is partnered with Merck outside the country. Sac-TMT got its domestic go-ahead in previously treated TNBC in 2024 after the China-only optiTROP-Breast01 trial showed the drug improved PFS by 69% and OS by 47% versus chemo.
Strong first-line NSCLC findings recently unveiled from the Chinese OptiTROP-Lung05 trial drew excitement among doctors and analysts. Leerink Partners analysts have projected the Kelun/Merck drug could reach $10 billion in 2035 global sales. In the first quarter of 2026, Gilead’s Trodelvy sales increased 37% year over year to $420 million.