Merck gets saci in ovarian
Sacituzumab tirumotecan joins raludotatug deruxtecan on the ovarian cancer pivotal stage.
Sacituzumab tirumotecan joins raludotatug deruxtecan on the ovarian cancer pivotal stage.
Ovarian cancer will soon become the latest disease Merck & Co is targeting with its huge pivotal programme for the Kelun-originated TROP2-targeting ADC sacituzumab tirumotecan. The phase 3 TroFuse-022 study is set to begin next month, according to a new listing on clinicaltrials.gov.
On the face of it, this sets up a clash with another Merck ADC, the anti-CDH6 raludotatug deruxtecan, which came via a mega-licensing deal with Daiichi Sankyo. That project is already in the phase 2/3 Rejoice-Ovarian01 trial in this setting. However, a closer look shows some key differences.
The biggest is that TroFuse-022 will enrol platinum-sensitive patients, while Rejoice-Ovarian01 has recruited platinum-resistant patients.
Platinum-sensitive disease is defined as cancer that has relapsed at least six months after the end of platinum-based chemotherapy, while platinum-resistant cancer has relapsed less than six months after chemo. Platinum-resistant disease has a poorer prognosis and limited treatment options.
In the platinum-sensitive setting, TroFuse-022 will enrol second-line subjects and compare saci-T as maintenance therapy, with or without Avastin, versus Avastin alone. The primary efficacy endpoint is progression-free survival.
Rejoice-Ovarian01, meanwhile, has recruited second-line or later platinum-resistant patients. The first part of the trial aims to nail down ralu-dxd’s recommended dose, while the second part will compare the asset against investigator’s choice of chemotherapy, and will primarily measure PFS and overall response rate.
Saci-T & raludotatug-dxd in ovarian cancer
Sacituzumab tirumotecan | Raludotatug deruxtecan | |
|---|---|---|
| Description | Anti-TROP2 ADC | Anti-CDH6 ADC |
| Originator | Kelun | Daiichi Sankyo |
| Trial | TroFuse-022 | Rejoice-Ovarian01* |
| Sponsor | Merck & Co | Daiichi Sankyo |
| Setting | 2rd-line maintenance, platinum-sensitive (after platinum-based doublet chemo) | 2nd-line, platinum-resistant |
| Regimen | +/- Avastin, vs Avastin | Monotherapy, vs chemo |
| Primary completion | Apr 2030 | Dec 2027 |
Note: *phase 2/3. Source: OncologyPipeline & clinicaltrials.gov.
The TROP2 field already has two approved drugs, but Gilead’s Trodelvy is only indicated for breast cancer. There are two investigator-sponsored phase 2 trials of that ADC ongoing in ovarian cancer, according to OncologyPipeline, but this doesn’t appear to be a priority for Gilead, which is focused on breast, endometrial and lung cancers – most recently small-cell.
The other big TROP2 players are AstraZeneca and Daiichi, whose Datroway recently secured its first FDA nod, in second-line breast cancer. In ovarian cancer that project is being tested alongside Astra’s selective PARP1 inhibitor saruparib in the phase 2 Petra trial.
And Jiangsu HengRui’s anti-TROP2 ADC SHR-A1921 is in a Chinese phase 3 study in platinum-resistant disease.
Merck is testing saci-T in a wide range of tumours, including breast, NSCLC, endometrial and cervical cancers, with Kelun also carrying out a slew of Asia-focused studies. The asset recently got its first approval, in China, but has yet to be filed in the US.
Meanwhile, there are no CDH6-targeting therapies approved, and ralu-dxd is the most advanced in this class. Various assets are in early-stage solid tumour trials, including OnCusp Therapeutics, whose ADC CUSP06 is in a phase 1 and was recently granted fast-track designation in platinum-resistant ovarian cancer.
This story has been updated to reflect the fact that TroFuse-022 is a maintenance trial.
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