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临床试验/NL-OMON48590
NL-OMON48590撤回2 期

A Phase 1/2 Study of Oral LOXO-292 in Patients with Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors with RET Activation (LIBRETTO-001) - LOXO-RET-17001

oxo Oncology, Inc.0 个研究点目标入组 3 人开始时间: 待定最近更新:
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试验速览

阶段
2 期
状态
撤回
发起方
入组人数
3
研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型
Interventional

入排标准

年龄范围
12 至 99（—）

入选标准

  • •Inclusion Criteria for Dose Escalation:
  • •1. Patients with a locally advanced or metastatic solid tumor that:
  • •* Has progressed following standard therapy, or
  • •* Has not adequately responded to standard therapy, or
  • •* For which no standard therapy exists, or
  • •* Patients who decline standard therapy, or
  • •* In the opinion of the Investigator, are not candidates for, or would be unlikely to tolerate or derive
  • •significant clinical benefit from standard therapy.
  • •2. Any number of prior TKIs with anti-RET activity are allowed. Refer to Appendix A for examples of multikinase inhibitors (MKIs) with anti-RET activity. The specific agent(s), duration of treatment, clinical benefit and reason for discontinuation (e.g., PD, drug toxicity or intolerance) should be documented for all kinase inhibitors the patient has been exposed to.
  • •3. Evidence of a RET gene alteration in tumor and/or blood (e.g., gene rearrangement and/or mutation, excluding synonymous, frameshift or nonsense mutations), as identified through molecular assays, as performed for clinical evaluation. The RET alteration result should be generated from a laboratory with certification by CLIA, ISO/EIC, CAP, or other similar certification. The Sponsor should be contacted to discuss test results from labs where such certification is not clearly demonstrated to determine eligibility.
  • •* During dose escalation, a RET gene alteration is not required initially. The Sponsor*s preclinical data indicates that a LOXO-292 plasma level of 70 ng/mL is equivalent to the 50% inhibitory concentration (IC50) for RET (corrected for human plasma protein binding). Therefore, once a dose level is achieved that: (1) is associated with a DLT rate of <33%; (2) is deemed safe by the SRC; and
  • •(3) is associated with a minimum concentration (Cmin) of >70 ng/mL at steady state in *70% of
  • •patients in the same dosing cohort (e.g., 3/3, 3/4, 4/5, 5/6 patients, etc.), enrollment to subsequent
  • •dose levels during dose escalation will be restricted to patients with: (1) RET-fusion NSCLC; (2)
  • •MTC; (3) an advanced solid tumor that harbors a RET gene alteration (e.g., gene rearrangement
  • •and/or mutation, excluding synonymous, frameshift or nonsense mutations) or (4) with prior Sponsor
  • •approval, an advanced solid tumor with other evidence of increased RET activity, e.g., increased RET expression in the absence of mutation, with strong preclinical/clinical evidence for RET dependence.
  • •* A positive germline test for a RET mutation is acceptable for patients with MTC.
  • •* Local testing in a CLIA, ISO/IEC, CAP, or other similar certified laboratory is sufficient.
  • •* In all cases, an anonymized/redacted Molecular Pathology Report, or other report(s) describing tumor RET (and other) mutation analysis should be submitted to the Sponsor or designee during Screening.
  • •4. Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type.
  • •5. At least 18 years of age.
  • •* For countries and sites where approved, patients as young as 12 years of age may be enrolled.
  • •6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 with no sudden deterioration 2 weeks prior to the first dose of study treatment.
  • •7. Life expectancy of at least 3 months.
  • •8. Archived tumor tissue sample available.
  • •* Patients who do not have adequate archival tumor tissue available (see specific arc

排除标准

  • •Exclusion Criteria for Dose Escalation and Dose Expansion:
  • •1. For NSCLC patients, an additional known oncogenic driver. Examples include targetable mutation in EGFR, targetable rearrangement involving ALK or ROS1, or KRAS (dose expansion only). Such patients may be enrolled to Cohort 5 with prior Sponsor approval.
  • •2. Investigational agent or anticancer therapy within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292. In addition, no concurrent investigational therapy is permitted.
  • •* Refer to Section 6.3.2 of the main protocol for allowable concurrent therapies.
  • •* 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.
  • •3. Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of
  • •LOXO-292.
  • •4. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study
  • •treatment, 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.
  • •5. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
  • •6. Symptomatic primary central nervous system (CNS) tumor or metastases; symptomatic leptomeningeal carcinomatosis; untreated spinal cord compression.
  • •Exception: Patients with CNS primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms have been stable for 14 days prior to the first dose of LOXO-292, there has been no increase in steroid dose for 14 days prior to the first dose of LOXO-292 to manage CNS symptoms, and no CNS surgery or radiation has been performed for 28 days (14 days after last radiation with stereotactic radiosurgery [SRS]).
  • •7. 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 for heart rate (QTcF) >470 msec on at least 2/3 consecutive ECGs, and mean QTcF >470 msec on all 3 ECGs, during Screening. Correction of suspected drug-induced QTcF prolongation may be attempted at the Investigator*s discretion if clinically safe to do so.
  • •8. Active uncontrolled systemic bacterial, viral, or fungal infection, which in the opinion of the Investigator makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
  • •9. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
  • •10. Uncontrolled symptomatic hyperthyroidism or hypothyroidism.
  • •11. Uncontrolled symptomatic hypercalcemia or hypocalcemia.
  • •12. Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (refer to Appendix C of the main protocol).
  • •13. Current treatment with proton pump inhibitors (PPIs) (refer to Appendix F of the main protocol).
  • •* Treatment with PPIs must be stopped 1 or more weeks prior to the first dose of LOXO-292. For
  • •recommended alternatives, refer to Section 6.3.3 of the main protocol).

研究者

发起方
oxo Oncology, Inc.

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