- |||||||||| TA0953/HM06, a Novel RET-specific Inhibitor Effective in Extracranial and CNS Disease Models of NSCLC with RETfusions (Hall C7) - Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_745;
P1/2
TAS0953/HM06 was more effective than selpercatinib at decreasing CNS disease and extending survival, at a dose that produced comparable suppression of tumor growth in extracranial disease models. TAS0953/HM06 represents a promising new therapeutic option for patients with RET fusions including those with brain metastasis and those resistant to first-generation selective RET inhibitors.
- |||||||||| Chylothorax and chylous ascites during RET tyrosine kinase inhibitor therapy. (Available On Demand; 67) - Apr 28, 2022 - Abstract #ASCO2022ASCO_2845;
Chylous effusions can emerge on treatment with certain MKIs or selective RET TKIs. Recognition of this potential side effect is key to prevent misattribution of worsening effusions to progressive malignancy and to motivate a better understanding of its biology and management.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Clinical, Journal: RET inhibition in novel patient-derived models of RET-fusion positive lung adenocarcinoma reveals a role for MYC upregulation. (Pubmed Central) - Dec 17, 2020
Moreover, cabozantinib was effective at reducing growth of a lung cancer PDX that was not responsive to RXDX-105...Notably, we identify MYC as a protein that is upregulated by RET expression and down-regulated by cabozantinib treatment, opening up potentially new therapeutic avenues for combinatorial targeting RET-fusion driven lung cancers. The novel RET fusion-dependent preclinical models described herein represent valuable tools for further refinement of current therapies and the evaluation of novel therapeutic strategies.
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Trial completion: Continued Access to RXDX-105 (clinicaltrials.gov) - Oct 1, 2020
P1, N=3, Completed,
The novel RET fusion-dependent preclinical models described herein represent valuable tools for further refinement of current therapies and the evaluation of novel therapeutic strategies. Active, not recruiting --> Completed
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
P1 data, Journal: A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105. (Pubmed Central) - May 15, 2020
Interestingly, the ORR varied significantly by the gene fusion partner (p<0.001, Fisher's exact test): 0% (95% CI 0% - 17%, n=0/20) with KIF5B (the most common upstream partner for RET fusion-positive NSCLC), and 67% (95% CI 30% - 93%, n=6/9) with non-KIF5B partners. The median duration of response in all RET fusion-positive NSCLCs was not reached (range 5 to 18+ months).
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
RXDX105 (STARLIGHT BALLROOM) - Feb 21, 2020 - Abstract #IASLCLCTT2020IASLC_LCTT_251;
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Enrollment closed, Trial completion date, Trial primary completion date: Continued Access to RXDX-105 (clinicaltrials.gov) - Nov 20, 2019
P1, N=3, Active, not recruiting,
In conclusion, our preclinical data suggest that agerafenib might be an effective therapeutic agent for NB treatment, both as a single-agent and in combination with chemotherapy. Recruiting --> Active, not recruiting | Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Dec 2019 --> Dec 2020
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Journal, MSi-H Biomarker: RET fusions in a small subset of advanced colorectal cancers at risk of being neglected. (Pubmed Central) - Nov 15, 2019
P1
RET rearranged and RET negative mCRCs were retrieved by systematic literature review and by taking advantage of three screening sources: (i) Ignyta's phase 1/1b study on RXDX-105 (NCT01877811), (ii) cohorts screened at two Italian and one South Korean Institutions and (iii) Foundation Medicine Inc...In the multivariable model, RET rearrangements were still associated with shorter OS [HR: 2.97; 95% CI, 1.25-7.07; P=0.014], while primary tumor location, RAS and BRAF mutations and MSI status were not. Though very rare, RET rearrangements define a new subtype of mCRC that shows poor prognosis with conventional treatments and is therefore worth of a specific management.
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Preclinical, Journal: The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo. (Pubmed Central) - Nov 7, 2019
RXDX-105 also showed enhanced efficacy in combination with 13-cis-retinoic acid, which is currently a component of maintenance therapy for children with high-risk neuroblastoma. Our results demonstrate that RXDX-105 shows promise as a novel therapeutic agent for children with high-risk and relapsed neuroblastoma.
- |||||||||| selpercatinib (LOXO-292) / Loxo Oncology, pralsetinib (BLU-667) / Blueprint Medicines, agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Clinical, Journal: Targeted Therapy For RET-Rearranged Non-Small Cell Lung Cancer: Clinical Development And Future Directions. (Pubmed Central) - Oct 3, 2019
Additionally, multi-kinase inhibition in RET-driven NSCLC patients showed concerning rates of high-grade toxicity, mainly induced by anti-VEGFR-kinase activity. Novel selective RET inhibitors like BLU-667, LOXO-292 and RXDX-105 have been recently investigated in early phase clinical trials showing promising efficacy with a manageable toxicity profile.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Review, Journal: Targeting RET-rearranged non-small-cell lung cancer: future prospects. (Pubmed Central) - Apr 10, 2019
Some data emerged about intracranial antitumor activity of BLU-667 and LOXO-292. If these novel drugs will achieve high activity in RET rearranged NSCLC, also these oncogene-addicted tumors can undergo a significant survival improvement.
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Trial completion, Trial completion date, Metastases: Study of RXDX-105, Potent RET Inhibitor in Patients With Advanced Lung Cancer and Other Solid Tumors (clinicaltrials.gov) - Feb 27, 2019
P1, N=143, Completed,
If these novel drugs will achieve high activity in RET rearranged NSCLC, also these oncogene-addicted tumors can undergo a significant survival improvement. Active, not recruiting --> Completed | Trial completion date: Jun 2019 --> Feb 2019
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Enrollment open, Phase classification: Continued Access to RXDX-105 (clinicaltrials.gov) - Feb 21, 2019
P1, N=4, Recruiting,
Active, not recruiting --> Completed | Trial completion date: Jun 2019 --> Feb 2019 Available --> Recruiting | Phase classification: PN/A --> P1
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
Phase classification: Continued Access to RXDX-105 (clinicaltrials.gov) - Jan 16, 2019
P=N/A, N=0, Available,
Available --> Recruiting | Phase classification: PN/A --> P1 Phase classification: P1 --> P=N/A
- |||||||||| agerafenib (RXDX-105) / Roche, Daiichi Sankyo
New P1 trial: Continued Access to RXDX-105 (clinicaltrials.gov) - Dec 21, 2018
P1, N=4, Recruiting,
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