Combining camonsertib with PARP inhibitors may be an effective strategy for treating advanced solid tumors, according to research presented at the AACR Annual Meeting 2023.
Researchers evaluated camonsertib, an ATR inhibitor, in combination with 1 of 3 PARP inhibitors — talazoparib, niraparib, or olaparib — in patients with advanced solid tumors. The patients were enrolled in a pair of phase 1/2 trials — TRESR (ClinicalTrials.gov Identifier: NCT04497116) and ATTACC (NCT04972110).
The researchers analyzed 107 patients from these trials. The patients had soft tissue sarcoma (n=6) as well as ovarian (n=22), breast (n=22), pancreatic (n=16), prostate (n=14), colorectal (n=7), bile duct (n=5), and other (n=15) cancers. The most commonly altered genes in this cohort were BRCA2 (n=35), ATM (n=28), and BRCA1 (n=21).
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At baseline, the patients had received a median of 3 prior lines of therapy (range, 2-4). Prior therapies included PARP inhibitors (39%), PD-L1 inhibitors (16%), and platinum chemotherapy (69%). Of the patients who had prior platinum treatment, 78% had platinum-resistant or -refractory disease.
On study, patients received camonsertib in combination with talazoparib (n=43), niraparib (n=29), or olaparib (n=35). Dosing varied. The dosing schedules chosen for further evaluation were:
- Camonsertib at 80 mg daily on days 5-7 plus talazoparib at 0.25 mg daily, 1 week on and 1 week off
- Camonsertib at 80 mg daily plus niraparib at 100 mg daily, 2 days on, 5 days off every week
- Camonsertib at 50 mg daily plus olaparib at 100 mg twice daily, 3 days on, 4 days off every week.
Dose-limiting toxicities with these dosing schedules included neutropenia (7%), thrombocytopenia (6%), febrile neutropenia (3%), and anemia (3%).
For all patients and all combinations, the clinical benefit rate (CBR) was 48%. The CBR, overall response rate (ORR), and molecular response rate (MRR) for each combination are shown in the table below.
|
Outcomes by Treatment Group |
|||
|
Combination |
CBR |
ORR |
MRR |
|
Camonsertib plus talazoparib |
46% |
10% |
65% |
|
Camonsertib plus niraparib |
59% |
18% |
79% |
|
Camonsertib plus olaparib |
41% |
10% |
56% |
The 3 regimens produced responses across tumor types and mutation types. Responses were seen regardless of the combination used, prior PARP inhibitor exposure, or platinum sensitivity.
However, patients with late-line ovarian cancer derived the most benefit from treatment, said study presenter Timothy A. Yap, MBBS, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
In the 19 patients with late-line ovarian cancer, the ORR was 32%, the CBR was 58%, and the median progression-free survival was about 7 months. These outcomes compare “favorably” to current therapeutic options for ovarian cancer patients, Dr Yap said.
“Low-dose intermittent regimens of camonsertib and different PARP inhibitor combinations were safe, with transient hematological events,” Dr Yap said in closing. “Durable antitumor activity was encouraging. This approach could represent a novel strategy in areas of unmet clinical need.”
Disclosures: This research was supported by Repare Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Yap TA, Yadav S, Herzberg B, et al. Safety and efficacy of three PARP inhibitors (PARPi) combined with the ataxia telangiectasia- and Rad3-related kinase inhibitor (ATRi) camonsertib in patients (pts) with solid tumors harboring DNA damage response (DDR) alterations. AACR 2023. April 14-19, 2023. Abstract CT018.
This article originally appeared on Cancer Therapy Advisor
