Summary

for people ages 12 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

This is a Phase 1, open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of LOXO-292 administered orally to patients with advanced solid tumors, including RET-fusion non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other tumors with increased RET activity.

Official Title

A Phase 1 Study of Oral LOXO-292 in Patients With Advanced Solid Tumors, Including RET-Fusion Non-Small Cell Lung Cancer, Medullary Thyroid Cancer, and Other Tumors With Increased RET Activity

Details

The trial will be conducted in 2 parts: dose escalation (Part 1) and dose expansion (Part 2). During Part 1, patients with advanced NSCLC, advanced MTC or other advanced solid tumors are initially eligible if the tumor has progressed following or has not adequately responded to standard therapy, or if the patient is intolerant of, unlikely to benefit from or refuses standard therapy. During Part 2, patients with NSCLC, MTC or other advanced solid tumor that harbors a RET gene alteration or other evidence of increased RET activity are eligible.

Keywords

Non-Small Cell Lung Cancer Medullary Thyroid Cancer Colon Cancer Solid Tumor LOXO-292 KIF5B-RET M918T CCDC6-RET RET-PTC1 NCOA4-RET RET-PTC RET-PTC3 RET-PTC4 PRKAR1A-RET RET-PTC2 GOLGA5-RET RET-PTC5 ERC1-RET KTN1-RET RET-PTC8 HOOK3-RET PCM1-RET TRIM24-RET RET-PTC6 TRIM27-RET TRIM33-RET RET-PTC7 AKAP13-RET FKBP15-RET SPECC1L-RET TBL1XR1-RET BCR-RET FGRF1OP-RET RFG8-RET RET-PTC9 ACBD5-RET MYH13-RET CUX1-RET KIAA1468-RET FRMD4A-RET SQSTM1-RET AFAP1L2-RET PPFIBP2-RET EML4-RET PARD3-RET G533C C609F C609G C609R C609S C609Y C611F C611G C611S C611Y C611W C618F C618R C618S C620F C620R C620S C630R C630Y D631Y C634F C634G C634R C634S C634W C634Y K666E E768D L790F V804L V804M A883F S891A R912P CLIP1-RET Y806C RET fusion RET alteration RET mutation RET rearrangement RET translocation Neoplasms by Site Neoplasms Lung Neoplasms Carcinoma, Non-Small-Cell Lung Cancer of Lung Cancer of the Lung Lung Cancer Neoplasms, Lung Neoplasms, Pulmonary Pulmonary Cancer Pulmonary Neoplasms Respiratory Tract Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Papillary Thyroid Cancer Thyroid Diseases Thyroid Neoplasms Cancer of the Thyroid Cancer of Thyroid Neoplasms, Thyroid Thyroid Ademona Thyroid Cancer Thyroid Carcinoma Endocrine System Diseases Endocrine Gland Neoplasms Head and Neck Neoplasms Thoracic Neoplasms CNS tumor Primary CNS tumor Cancer of Colon Cancer of the Colon Colon Neoplasms Colonic Cancer Neoplasms, Colonic Malignant tumor of Breast Mammary Cancer Mammary Carcinoma, Human Mammary Neoplasm, Human Neoplasms, Breast Tumors, Breast Human Mammary Carcinoma Malignant Neoplasm of Breast Breast Carcinoma Breast Tumors Cancer of the Breast Breast Neoplasms Breast Cancer Colonic Neoplasms Carcinoma, Neuroendocrine

Eligibility

For people ages 12 years and up

Key Inclusion Criteria:

Diagnosis during Dose Escalation (Part 1)

  • Patients with a locally advanced or metastatic solid tumor that progressed following standard therapy, or has not adequately responded to standard therapy, or for whom no standard therapy exists, or who decline standard therapy, or in the opinion of the Investigator, is not a candidate for, or would be unlikely to tolerate or derive significant clinical benefit from standard therapy.
  • Once a safe dose level is achieved that is consistent with inhibiting RET, patients must have advanced NSCLC, MTC or other advanced solid tumor with evidence of RET alteration or other evidence of increased RET activity in tumor tissue and/or blood.
  • Any number of prior TKIs.
  • Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type.
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
  • Adequate hematologic, hepatic and renal function.
  • Life expectancy of at least 3 months.

Inclusion Criteria:

Diagnosis during Dose Expansion (Part 2)

  • Patients with a locally advanced or metastatic solid tumor that progressed following standard therapy, or has not adequately responded to standard therapy, or for whom no standard therapy exists, or who decline standard therapy, or in the opinion of the Investigator, is not a candidate for, or would be unlikely to tolerate or derive significant clinical benefit from standard therapy.
  • Group 1: Advanced RET-fusion NSCLC with ≥ 1 prior tyrosine kinase inhibitor (TKI) that inhibit RET
  • Group 2: Advanced RET-fusion NSCLC with no prior TKI that inhibits RET
  • Group 3: Advanced RET-mutant MTC with ≥ 1 prior TKI that inhibit RET
  • Group 4: Advanced RET-mutant MTC with no prior TKI that inhibits RET
  • Group 5: Disease not measurable, other RET-altered tumors, other RET alterations,cfDNA positive for RET alteration with tumor discordant or negative, RET mutation-negative MTC with any number of prior TKIs that inhibit RET
  • For MTC: PD within the previous 14 months as defined by RECIST 1.1.
  • Any number of prior TKIs.
  • At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type, not previously irradiated and not chosen for biopsy during the screening period. Patients without RECIST 1.1 or RANO measurable disease may be eligible for enrollment to Group 5.
  • ECOG score of 0, 1, or 2.
  • Adequate hematologic, hepatic and renal function.
  • Life expectancy of at least 3 months.

Key Exclusion Criteria (Dose Escalation and Dose Expansion):

  • For NSCLC patients, an additional known oncogenic driver. Examples include targetable mutation in EGFR, targetable rearrangement involving ALK, or ROS1, or KRAS (for dose expansion only). Such patients may be enrolled to Cohort 5 with prior Sponsor approval.
  • Investigational agent or anticancer therapy within 5 half-lives or 2 weeks (14 days)prior to planned start of LOXO-292. LOXO-292 may be started within less than 5 half-lives or 2 weeks of prior therapy if considered by the Investigator to be safe and within the best interest of the patient, with prior Sponsor approval.
  • Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of LOXO-292.
  • Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292, with the exception of patients receiving radiation to more than 30%of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment.
  • Symptomatic primary CNS tumor or metastases (stable CNS tumor/metastases is allowed).
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 or prolongation of the QT interval corrected (QTcF) > 470 msec.
  • Required treatment with certain strong CYP3A4 inhibitors or inducers.

Locations

  • UCSD Medical Center accepting new patients
    La Jolla California 92093-0698 United States
  • City of Hope accepting new patients
    Duarte California 91010 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Loxo Oncology, Inc.
ID
NCT03157128
Phase
Phase 1
Study Type
Interventional
Last Updated
June 1, 2018