SELPERCATINIB for RET fusion-positive solid tumor | Medullary thyroid cancer | Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 7. Phase 1: Life expectancy of at least 3 months."}
• {"criterion_text":"- 8. Phase 1: Archived tumor tissue sample available."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 1. Phase 2: Cohorts 1 and 3: failed or intolerant to standard of care. Cohorts 2 and 4 without prior standard first line therapy."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 5. Part 2: Cohort 4: radiographic PD within the previous 14 months."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 12. Phase 1: Ability to swallow capsules and comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation."}
• {"criterion_text":"- 13. Phase 1: Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 1 month following the last dose of study treatment."}
• {"criterion_text":"- 2. Phase 1: Prior MKIs with anti-RET activity are allowed."}
• {"criterion_text":"- 3. Phase 1: A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required."}
• {"criterion_text":"- 4. Phase 1: Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type."}
• {"criterion_text":"- 5. Phase 1: At least 18 years of age. - For countries and sites where approved, patients as young as 12 years of age may be enrolled."}

Exclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- 10. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug."}
• {"criterion_text":"- 11. Uncontrolled symptomatic hyperthyroidism or hypothyroidism."}
• {"criterion_text":"- 12. Uncontrolled symptomatic hypercalcemia or hypocalcemia."}
• {"criterion_text":"- 13. Pregnancy or lactation."}
• {"criterion_text":"- 14. Active second malignancy other than minor treatment of indolent cancers."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 2. Cohorts 1 to 5: Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 4. Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of selpercatinib."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- 1. Phase 1: MTD/RP2D.","definition_or_measurement_approach":"Phase 1 primary objective: To determine the MTD/recommended Phase 2 dose (RP2D)."}
• {"endpoint_text":"- 2. Phase 2: ORR based on RECIST 1.1 or RANO, as appropriate to tumor type, assessed by IRC.","definition_or_measurement_approach":"Phase 2 primary endpoint: Objective Response Rate (ORR) determined using RECIST 1.1 or RANO as appropriate to tumor type, assessed by an independent review committee (IRC)."}

Denmark

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

09-04-2024

Processing Time Days

21

Number Of Sites

1

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

15-04-2024

Processing Time Days

27

Number Of Sites

5

Number Of Participants

74

Germany

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

10-04-2024

Processing Time Days

22

Number Of Sites

2

Number Of Participants

16

Italy

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

13-05-2024

Processing Time Days

55

Number Of Sites

1

Number Of Participants

14

Spain

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

15-04-2024

Processing Time Days

27

Number Of Sites

3

Number Of Participants

21

Primary sponsor

Full Name

Loxo Oncology Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

codes:1,11,12,2,3,6,7,8,9

Third parties

• {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"Pharmacokinetics testing: blood and urine","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Imaging Endpoints II LLC","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes:1,11,12,2,3,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Omniseq Inc.","duties_or_roles":"Molecular Processing, Sequencing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"Pharmacogenomics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Travel arrangements and expense management","organisation_type":"Non-Pharmaceutical company"}