Express reduces the risk of disease progression of specific prostate cancers by 50%, and PARP inhibitors reach the primary clinical endpoint of phase 3

Clovis Oncology, editor of WuXi AppTec Content Team, today announced positive top-line results
from the TRITON3 Phase 3 clinical trial.
The analysis showed that its PARP inhibitor Rubraca (rucaparib) achieved the primary endpoint of the trial, that is, Rubraca significantly improved radiographically progression-free survival (rPFS)
in patients with metastatic castration-resistant prostate cancer (mCRPC) with BRCA or ATM mutations compared with the chemotherapy control group.
According to the press release, this is the first PARP inhibitor to significantly improve radiographic-progression-free survival in patients with mCRPC compared to chemotherapy
.
Clovis expects to submit a New Drug Application (sNDA) for use of this drug in a subpopulation of BRCA mutation patients with BRCA mutations to the US FDA in the first quarter of 2023 and discuss with the FDA the possibility of expanding the
scope of application of this drug.


Prostate cancer is the second most commonly diagnosed malignant tumor
in men worldwide.
The American Cancer Society (ACS) estimates that in 2022, an estimated 268,000 men in the United States will be diagnosed with prostate cancer
.
Most men have localized prostate cancer at the time of diagnosis, which can be treated
with surgery or radiation therapy.
When the disease metastasizes or spreads, it develops into mCRPC
.
The growth of prostate cancer cells is androgen-dependent, so patients are initially sensitive to androgen deprivation therapy (ADT), while patients who still develop disease progression after persistent ADT develop mCRPC
.
The 5-year survival rate for mCRPC patients is about 30%, while the overall survival in clinical trials is about 3 years, which is expected to be even smaller
in the real world.
About 19% of patients with mCRPC have BRCA or ATM mutations
.

Rubraca is an oral small molecule PARP1,2,3 inhibitor
.
PARP plays an important role in DNA damage repair, and by targeting PARP, Rubraca can cause tumor cells with homologous recombination repair defects to die
due to the accumulation of too much DNA damage.
Rubraca is approved in the United States for the treatment of recurrent ovarian cancer, with accelerated approval for the treatment of mCRPC patients
with BRCA mutations who have received prior therapy.

TRITON3 is a multicenter, open-label
Phase 3 clinical trial in which 405 patients were randomly assigned to receive either Rubraca or the chemotherapy of their choice (55% of the control patients were treated with docetaxel
).
The main objective of the trial was radio-free progression-free survival in patients with BRCA1, BRCA2, or ATM mutations who had undergone independent imaging evaluation (IRR
).
All enrolled patients had harmful mutations in BRCA and ATM and had received a next-generation targeted treatment for androgen receptors
.

The analysis showed that Rubraca had significant efficacy in subsets of patients with BRCA mutations
.
The median progression-free survival of imaging in patients in the Rubraca group (n=201) and control group (n=101) was 11.
2 and 6.
4 months, respectively (HR: 0.
50, 95% CI: 0.
36-0.
69, p<0.
0001),
respectively 。 Similar results were shown in the ITT population containing BRCA or ATM mutations (including all patients, n=405), with median radiographically progression-free survival of 10.
2 and 6.
4 months (HR: 0.
61, 95% CI: 0.
47-0.
80, p=0.
0003) in patients in the Rubraca group (n=270) and control (n=135),
respectively 。 On the other hand, in the exploratory analysis of subsets of patients with ATM mutations (n=103), the median radiographic-progression-free survival of patients in the Rubraca group (n=69) and the control group (n=34) was 8.
1 and 6.
8 months, respectively (HR: 0.
97, 95% CI: 0.
59-1.
52, p=0.
8421).


In terms of safety, the adverse effects observed in the trials were consistent
with Rubraca's labeling.
The rate at which trials were terminated in Rubraca versus control due to treatment-related adverse effects (TEAE) was 14.
8% versus 21.
5%,
respectively.

"We believe the positive results of TRITON3 further confirm that Rubraca can be a treatment option
for patients with homologous recombination repair defective tumors mCRPC.
" We look forward to submitting these data
to U.
S.
regulators in Q1 2023.
" Not only does this drug provide a potential treatment option for eligible early stage patients, but it is also the first PARP inhibitor to significantly improve progression-free survival of imaging compared to chemotherapy
.
Chemotherapy remains the standard of care
for these patients today.
Mr.
Patrick J.
Mahaffy, President and Chief Executive Officer of Clovis, said
.

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