FDA Approves Ivosidenib CDx for IDH1-Mutated Cholangiocarcinoma Detection

To accompany a newly approved targeted therapy for IDH1-mutated cholangiocarcinoma, the Oncomine Dx Target Test has been approved as a companion diagnostic.

The FDA has granted approval to the Oncomine Dx Target Test developed by Thermo Fisher Scientific as a companion diagnostic to identify patients with IDH1-mutated cholangiocarcinoma who may be eligible for treatment with the newly-approved targeted therapy ivosidenib (Tibsovo).1

The Oncomine Dx Target Test is a next-generation (NG)-based test which has been shown to provide robust and reproducible results in the IDH1 gene, which is associated with cholangiocarcinoma. The Oncomine Dx Target Test is also FDA approved for the detect of gene mutation in non–small cell lung cancer (NSCLC). Outside of the US, the test is approved in 15 other countries.

"With the FDA approval of Oncomine Dx Target Test as a companion diagnostic for TIBSOVO, healthcare providers across the US can now match patients with this critically needed therapy," said Garret Hampton, president of Clinical Next-Generation Sequencing and Oncology at Thermo Fisher Scientific, in a press release. "Advances in genetic profiling through NGS have enabled identification of an increasing number of cancer-driving genomic variations, opening the door for the development of more targeted treatment options. By continuing to work with our pharmaceutical partners to co-develop diagnostics for these life-changing therapies and expanding the clinical utility of our tests, we hope to help more cancer patients around the world receive more targeted and effective treatment."

Compared with a single-gene test used to detect EGFR mutations in NSCLC, Oncomine Dx Target Test had a 90% success rate versus the 28% success rate with single-gene testing. The Oncomine Dx Target Test.2 In detection of IDH1-mutant tumors, specifically, the assay showed sensitivity, reproducibility, and accuracy in detection of IDH1 R132 variants from 10 ng of DNA extracted from FFPE CC specimens, in an analysis of the phase 3 ClarIDHy study.3

The ClarIDHy study (NCT0298985) led to the recent FDA approval of ivosidenib tablets for the treatment of patients with IDH1-mutant cholangiocarcinoma. In the study, treatment with ivosidenib achieved a median PFS of 2.7 months (1.6-4.2) versus 1.4 months (1.4-1.6), respectively. The PFS improvement with ivosidenib was statistically significant (HR, 0.37; 95% CI, 0.25, 0.54], P <.001).4

Ivosidenib also appeared with be a safe treatment for IDH1-mutated cholangiocarcinoma. The most common treatment-emergent AEs (TEAEs) in the ivosidenib or placebo arms, respectively included nausea (38% vs 28.8%), abdominal pain (22.3% vs 15.3%), diarrhea (33.1% vs 16.9%), fatigue (28.9% vs 16.9%), cough (21.7% vs 8.5%), decreased appetite (21.7% vs 18.6%), ascites (19.9% vs 15.3%), vomiting (19.9% vs 18.6%), and anemia (18.1% vs 5.1%). Fifty-three percent of patients experienced grade 3 TEAEs. The most common grade 3 or higher TEAEs in in the ivosidenib or placebo arms, respectively were ascites (9.0% vs 6.8%, respectively), blood bilirubin increase (5.4% vs 1.7%), and anemia (7.2% vs 0%).

With the use of the Oncomine Dx Target Test, the aim is to find even more patients in real-world clinics to benefit from the survival-extending capabilities of ivosidenib.

"With the FDA approval of Oncomine Dx Target Test as a companion diagnostic for Tibsovo, healthcare providers across the United States can now match patients with this critically needed therapy," said Garret Hampton, president of clinical next-generation sequencing and oncology at Thermo Fisher Scientific, in a press release.1 "Advances in genetic profiling through NGS have enabled identification of an increasing number of cancer-driving genomic variations, opening the door for the development of more targeted treatment options. By continuing to work with our pharmaceutical partners to co-develop diagnostics for these life-changing therapies and expanding the clinical utility of our tests, we hope to help more cancer patients around the world receive more targeted and effective treatment."

References:

1. FDA approves NGS-based companion diagnostic for previously treated IDH1-mutated cholangiocarcinoma. News release. Thermo Fisher Scientific. August 25, 2021. Accessed August 25, 2021. https://bit.ly/3mIqxUm

2. Sakaguchi T, Iketani A, Furuhashi K, et al. Comparison of the analytical performance between the Oncomine Dx Target Test and a conventional single gene test for epidermal growth factor receptor mutation in non-small cell lung cancer. Thorac Cancer. 2021;12:462-467. doi: 10.1111/1759-7714.13767

3. Aiyer AR, Nater T, Brentnall M, et al. Performance characteristics of the Oncomine™ Dx Target Test for the detection of IDH1 R132 variants from formalin-fixed, paraffin-embedded (FFPE) cholangiocarcinoma samples. Presented at: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. Abstract 772.

4. Zhu AX, Macarulla T, Javle MM, et al. Final results from ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation. J Clin Oncol. 2021;39(suppl 3):266. doi:10.1200/JCO.2021.39.3_suppl.266