Tolmar Announces Expanded Indication for Rubraca® (rucaparib) First and Only PARP Inhibitor to Outperform Docetaxel in a Head-to-Head Phase 3 Trial
- FDA approval is based on the positive results of TRITON3, a Phase 3, multicenter, open-label, randomized clinical trial of Rubraca® (rucaparib) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients
- This approval makes rucaparib an earlier treatment option for eligible mCRPC patients1
Intended for the Healthcare Media
BUFFALO GROVE, Ill., Dec. 19, 2025 /PRNewswire/ -- Tolmar, Inc. (Tolmar) today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded indication for Rubraca® (rucaparib), enabling its use prior to chemotherapy for eligible patients with metastatic castration-resistant prostate cancer (mCRPC). The approval is supported by the pivotal TRITON3 Phase 3 trial, which demonstrated that Rubraca is the first and only PARP inhibitor to exceed the efficacy of docetaxel in a direct, head-to-head comparison, marking a significant evolution in treatment sequencing for patients with DNA damage repair (DDR)-deficient tumors.
"This approval reflects a breakthrough moment for patients and for precision oncology," said Anil D'Souza, Chief Executive Officer of Tolmar. "For years, oncologists have relied on docetaxel as an important therapy in this setting. Now, TRITON3 has shown that Rubraca can not only move ahead of chemotherapy but outperform it—supported by clear genomic rationale and superior progression-free survival. Bringing Rubraca earlier in the treatment journey offers physicians a more targeted approach for patients with BRCA mutated prostate cancer."
The TRITON3 study is a Phase 3, multicenter, open-label, randomized trial of rucaparib in chemotherapy-naïve mCRPC patients who had been previously treated with an androgen receptor directed therapy. The study enrolled 405 patients with a mutation in BRCA or ATM who were randomized to rucaparib or the control group, which consisted of physician's choice of docetaxel, abiraterone acetate, or enzalutamide. Approximately 55% of the patients in the control arm received docetaxel. The primary endpoint was radiographic progression-free survival (rPFS) by independent radiology review (IRR), in patients with mutations in BRCA1, BRCA2 or ATM. TRITON3 was designed as a Phase 3 trial to confirm and expand the efficacy data from TRITON2 in an earlier treatment setting in mCRPC against a relevant control arm. Patients were selected for therapy based on an FDA-approved companion diagnostic for rucaparib.
Key findings include:
- Superiority in Radiographic Progression-Free Survival (rPFS):
Rubraca achieved a statistically significant improvement in rPFS vs. the control arm, delivering a median rPFS of 11.2 months vs. 6.4 months , HR 0.50 - In a sub-analysis of Rubraca vs Docetaxel, the rPFS was 11.2 months vs. 8.3 months with docetaxel in the BRCA subgroup
- Compelling Genomically Driven Benefit:
Patients with BRCA mutations demonstrated the strongest response, showing a ~50% reduction in risk of progression or death vs. docetaxel - Rubraca Tolerability Profile:
The safety profile of Rubraca observed in TRITON3 was consistent with previous studies. In TRITON3, the discontinuation rate for TEAEs was 14.8% for Rubraca-treated patients and 21.5% for the control arm
Prostate cancer is the most diagnosed cancer in U.S. men, with an estimated 313,780 new cases diagnosed in 2025.2 Approximately 10 to 20 percent of patients progress to castration-resistant prostate cancer, an incurable disease, within five years of diagnosis.3 The vast majority have metastases at diagnosis or develop metastases within two years.3 Of these, an estimated 13% have BRCA-mutated mCRPC,4 a disease characteristic associated with a poor prognosis.5 Men with mCRPC and the presence of a germline BRCA2 mutation, a prognostic marker, have more aggressive disease and poorer survival.6 While less common in prostate cancer, germline mutations in BRCA1 are also associated with more aggressive disease6. mCRPC generally responds to initial androgen deprivation therapy.7 However, most patients will inevitably develop treatment resistance.7
Rubraca® (rucaparib) U.S. Prostate Cancer FDA-Approved Indication
INDICATION
RUBRACA® (rucaparib) is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy. Select patients for therapy based on an FDA-approved companion diagnostic for RUBRACA.
SELECT IMPORTANT SAFETY INFORMATION
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur in patients treated with RUBRACA, and are potentially fatal adverse reactions. In 2141 treated patients with ovarian and prostate cancer, MDS/AML occurred in 34 patients (1.6%), including those in long term follow-up. Of these, 14 occurred during treatment or during the 28-day safety follow-up (0.7%).
The duration of RUBRACA treatment prior to the diagnosis of MDS/AML ranged from < 2 months to approximately 72 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing chemotherapy regimens and/or other DNA damaging agents.
In ARIEL3, of patients with ovarian cancer associated with a germline and/or somatic BRCA mutation who were treated with RUBRACA, MDS/AML occurred in 9 out of 129 (7%) patients treated with RUBRACA and 4 out of 66 (6%) patients treated with placebo. The duration of therapy with RUBRACA in patients who developed secondary MDS/cancer therapy-related AML varied from 1.2 to 4.7 years.
In TRITON3, MDS/AML occurred in 2 out of 201 patients (1%) with a BRCA mutation treated with RUBRACA. The duration of therapy with RUBRACA in patients who developed secondary MDS/cancer therapy-related AML varied from 1.4 to 2.3 years.
Do not start RUBRACA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt RUBRACA or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue RUBRACA.
Based on findings from genetic toxicity and animal reproduction studies, RUBRACA can cause fetal harm. Advise male patients with female partners of reproductive potential or who are pregnant to use effective methods of contraception during treatment and for 3 months following last dose of RUBRACA. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of RUBRACA.
Most common adverse reactions of patients with BRCA-mutated mCRPC treated with RUBRACA in TRITON3 (≥10%, Grade 1-4) were fatigue/asthenia (61%), musculoskeletal pain (53%), nausea (51%), decreased appetite (34%), diarrhea (31%), constipation (31%), vomiting (25%), dyspnea (19%), dysgeusia (18%), edema (18%), abdominal pain (17%), dizziness (16%), weight decreased (16%), rash (13%), headache (12%), peripheral neuropathy (12%), photosensitivity reaction (12%), and urinary tract infection (10%).
Most common select laboratory abnormalities of patients with BRCA-mutated mCRPC treated with RUBRACA in TRITON3 (≥ 25%, Grade 1-4) were increased ALT (68%), decreased neutrophils (67%), decreased phosphate (64%), decreased hemoglobin (60%), increased AST (59%), increased creatinine (56%), increased glucose (45%), decreased lymphocytes (43%), decreased sodium (35%), decreased platelets (34%), and increased calcium (29%).
Most common adverse reactions of patients with BRCA-mutated mCRPC treated with RUBRACA in TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), decreased appetite (28%), rash (27%), constipation (27%), vomiting (22%), and diarrhea (20%).
Most common laboratory abnormalities of patients with BRCA-mutated mCRPC treated with RUBRACA in TRITON2 (≥ 35%; Grade 1-4) were increased ALT (69%), decreased leukocytes (69%), decreased phosphate (68%), decreased absolute neutrophil count (62%), decreased hemoglobin (59%), increased alkaline phosphatase (44%), increased creatinine (43%), decreased lymphocytes (42%), increased triglycerides (42%), decreased platelets (40%), and decreased sodium (38%).
Concomitant administration of RUBRACA with CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates can increase the systemic exposure of these substrates, which may increase the frequency or severity of adverse reactions of these substrates. If concomitant administration is unavoidable between RUBRACA and substrates of these enzymes where minimal concentration changes may lead to serious adverse reactions, decrease the substrate dosage in accordance with the approved prescribing information.
If concomitant administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing the frequency of international normalized ratio (INR) monitoring.
Full Prescribing Information available at: https://www.rubracahcp.com.
For medical information inquiries within the U.S., contact pharma& at [email protected].
You may report adverse events to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Alternatively, to report an adverse event or reaction, contact pharma& at [email protected].
To report a product complaint, contact pharma& at [email protected]
About Tolmar Inc. (tolmar.com)
Tolmar is a fully integrated specialty pharmaceutical company focused on the development, manufacturing, and commercialization of specialty pharmaceuticals across multiple therapeutic areas, including Oncology, Urology, and Endocrinology. Tolmar's product development and manufacturing facilities are based in Northern Colorado and its executive offices and commercial headquarters are based in Buffalo Grove, Illinois.
Tolmar cautions that any forward-looking statements or projections made, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Tolmar does not undertake to update or revise any forward-looking statements
Tolmar Media Contact:
[email protected]
RUBRACA® is a registered trademark of pharma& Schweiz GmbH, used under license by Tolmar.
References
1 Rucaparib USPI. https://www.rubracahcp.com/wp-content/uploads/2024/12/RubracaUSPI.pdf Accessed December 2025.
2Surveillance, Epidemiology, and End Results, National Cancer Institute. Cancer Stat Facts: Prostate Cancer. Available at: https://seer.cancer.gov/statfacts/html/prost.html Accessed November 2025
3 Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180–1192
4 Olmos, D. et al. Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes Annals of Oncology, Volume 35, Issue 5, 458 – 472
5 Messina C et al. BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications. J Oncol. 2020 Sep 7;2020:4986365. doi: 10.1155/2020/4986365. PMID: 32963528; PMCID: PMC7492871
6 Castro et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. Journal of Clinical Oncology. Available at: https://ascopubs.org/doi/10.1200/JCO.2012.43.1882 Accessed October 2025.
7 Kulasegaran, T., Oliveira, N. Metastatic Castration-Resistant Prostate Cancer: Advances in Treatment and Symptom Management. Current Treatment Options in Oncology. Available at: https://doi.org/10.1007/s11864-024-01215-2 Accessed November 2025.
8 ARIEL3 (NCT01968213): The safety of RUBRACA for the maintenance treatment of patients with BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer was investigated in ARIEL3.
9 TRITON2 (NCT02952534): The safety of RUBRACA for the treatment of BRCA-mutated mCRPC after Androgen Receptor-directed Therapy and Chemotherapy was evaluated in TRITON2.
10 TRITON3 (NCT02975934): The safety of RUBRACA for the treatment of BRCA-mutated mCRPC after progression on Androgen Receptor-directed Therapy.
SOURCE TOLMAR
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