A Phase 1/2 study on the effects of LOXO-292 (study drug) in patients with advanced solid tumors.

Phase 1

• Conditions: Male or female patients age 12 years or older with a locally advanced or metastatic solid tumor with evidence of a RET gene alteration in tumor and/or blood.; MedDRA version: 21.1Level: PTClassification code: 10027105Term: Medullary thyroid cancer Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code: 10065252Term: Solid tumor Class: 10029104; MedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-507702-13-00
• Lead Sponsor: oxo Oncology Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-06
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 857

Inclusion Criteria

1. Phase 1: Patients with a locally advanced or metastatic solid tumor who: - have progressed on or are intolerant to standard therapy, or - no standard therapy exists, 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, or - decline standard therapy., 6. Phase 1: Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 (age = 16 years) or Lansky Performance Score (LPS) = 40% (age < 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment., 7. Phase 1: Life expectancy of at least 3 months., 8. Phase 1: Archived tumor tissue sample available., 9. Phase 1: Adequate hematologic status, defined as: - Absolute neutrophil count (ANC) = 1.0.10^9/L not requiring growth factor support for at least 7 days prior to treatment, and - Platelet count = 75.10^9/L not requiring transfusion support for at least 7 days prior to treatment, and - Hb = 9 g/dL not requiring transfusion support or erythropoietin for at least 7 days prior to treatment., 1. Phase 2: Cohorts 1 and 3: failed or intolerant to standard of care. Cohorts 2 and 4 without prior standard first line therapy., 2. Phase 2: Cohorts 1-4: enrollment will be restricted to patients with evidence of a RET gene alteration in tumor (i.e., not just blood) as defined in Table 3., 3. Phase 2: However, a positive germline DNA test for a RET gene mutation as defined in Table 3 3 is acceptable in the absence of tumor tissue testing for patients with MTC., 4. Phase 2: Cohorts 1-4: at least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated (unless PD for the irradiated lesion[s] has been radiographically documented)., 5. Part 2: Cohort 4: radiographic PD within the previous 14 months., 6. Phase 2: Cohort 6: Patients who otherwise are eligible for Cohorts 1-5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval. Note: Examples of RET inhibitors may include TPX0046, pralsetinib (BLU667), or BOS172739., 10. Phase 1: Adequate hepatic function, defined as: - ALT and AST = 2.5 ULN or = 5 ULN with documented liver involvement (such as liver metastasis or a primary biliary tumor), and - Total bilirubin = 1.5 ULN or = 3 ULN with documented liver involvement (patients with Gilbert's Disease may be enrolled with prior Sponsor approval)., 7. Part 2: Cohort 5: Patients who otherwise are eligible for: - Cohorts 1-4 without measurable disease; - MTC not meeting the requirements for Cohorts 3 or 4; - MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval; - cfDNA positive for a RET gene alteration not known to be present in a tumor sample., 11. Phase 1: Adequate renal function, with estimated glomerular filtration rate = 30 mL/minute (up to 6 patients with an estimated glomerular filtration rate (eGFR) = 15 and < 30 will be allowed to enroll with Sponsor approval)., 12. Phase 1: Ability to swallow capsules and comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation., 13. Phase 1: Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and f

Exclusion Criteria

1. Phase 2 Cohorts 1-4: an additional validated oncogenic driver that could cause resistance to selpercatinib treatment. See Appendix C (Table 11 3) for examples., 10. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug., 11. Uncontrolled symptomatic hyperthyroidism or hypothyroidism., 12. Uncontrolled symptomatic hypercalcemia or hypocalcemia., 13. Pregnancy or lactation., 14. Active second malignancy other than minor treatment of indolent cancers., 15. History of hypersensitivity to any of the study drug capsule components, or any of the liquid suspension components (for patients that cannot swallow capsules)., 2. Cohorts 1 to 5: Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])., 3. Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of selpercatinib. In addition, no concurrent investigational anti-cancer therapy is permitted., 4. Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of selpercatinib., 5. 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., 6. 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., 7. Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Exception: Patients are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)., 8. Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) interval > 470 msec during Screening. Correction of suspected drug-induced QTcF prolongation may be attempted at the Investigator's discretion if clinically safe to do so., 9. Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment. Screening for chronic conditions is not required.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified