Attached files
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| 8-K - FORM 8-K - Ignyta, Inc. | d37148d8k.htm |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago Anna F. Farago, Manish Patel, Todd M. Bauer, Stephen V. Liu, Alexander Drilon, Jennifer Wheler,
Sai-Hong I. Ou, David Jackman, Daniel B. Costa, Pratik Multani, Zachary
Hornby, David Luo, Jonathan E. Lim, A. John Iafrate, and Alice
T. Shaw September 9, 2015
Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) Exhibit 99.1 |
 Disclosures: Consulting for Agios
Pharmaceuticals, Intervention
Insights, Cell Signaling Technology
MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago Ligand-mediated signaling TrkA/TrkB/TrkC Fusion oncogene signaling: ligand independent NTRK gene rearrangements in human malignancies |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago KM-12 is a human CRC line driven by a constitutively active TrkA fusion: TPM3-NTRK1 Entrectinib potently inhibits TrkA phosphorylation and downstream signaling Entrectinib induces in vivo
tumor regression and durable tumor stabilization In vitro
In vivo
xenograft Target TrkA TrkB TrkC ROS1 ALK IC50* (nM) 1.7 0.1 0.1 0.2 1.6 Entrectinib: pan-Trk inhibitor with in vitro and in vivo
activity * Biochemical kinase
assay Entrectinib |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago NTRK1 gene rearrangement in NSCLC patient identified by anchored multiplex polymerase chain reaction NTRK1 (NM_001007792.1) Chr1:156785542-156851642 Exon number: 10 SQSTM1 (NM_001142298) Chr5:179233388-179265077 Exon number:6 Chr5 Chr1 AMP PCR technique described in Zheng et al., Nat Med 2014 |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago Patient characteristics and clinical symptoms • Male, 45 years old when diagnosed with stage IV (T1bN1M1a) NSCLC, adenocarcinoma histology, in
November 2013 • 30 pack-year cigarette history, quit in 2000 • Developed progressive disease despite several lines of treatment, including chemotherapy and PD-1 inhibitor
• At the time of enrollment, the patient had ECOG PS 2 with baseline chest wall pain requiring PRN
narcotics, dyspnea at rest, and an oxygen requirement of 3L/min by nasal
cannula •
Staging head CT demonstrated 15-20 previously untreated brain metastases up
to 1.7 cm in diameter •
Enrolled on phase I clinical trial with entrectinib
at 400 mg/m 2 PO daily • Entrectinib was well tolerated, with possibly related AEs: • Dysgeusia, grade 1 • Paresthesias, grade 1 • Fatigue, grade 2 • Within three weeks of starting treatment, the patient reported resolution of pain and dyspnea, and no
longer required supplemental oxygen |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago Baseline (Day -7) Day 26: -47%
Day 155:
-77.3% Partial response by RECIST 1.1 at four weeks and ongoing |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago Complete response of all brain metastases Baseline (Day -7) Day 26 Day 155 |
 MINI30.09 – Clinical response to entrectinib in a patient with NTRK1-rearranged non-small cell lung cancer (NSCLC) - Farago Conclusions: • Entrectinib caused rapid and clinically significant improvement in a patient with NSCLC harboring an NTRK1 gene rearrangement. • The patient experienced resolution of baseline symptoms related to disease, including
pain, dyspnea, and hypoxia.
• Entrectinib was well tolerated with minimal side effects. • The response is durable and ongoing, with current duration of response 4.1 months.
• Entrectinib caused complete response of previously untreated brain metastases in this patient, indicating potent CNS penetration and activity. • Entrectinib may be an effective therapy for tumors harboring NTRK
gene rearrangements, including those with CNS involvement. |