A PHASE 1/2 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

JRCT ID: jRCT2051220060

Registered date:02/07/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced Solid Tumors, Including RET-Fusion Non Small Cell Lung Cancer, Medullary Thyroid Cancer, an
• Date of first enrollment: 03/07/2018
• Target sample size: 25
• Countries of recruitment: United States,Japan,Australia,Japan,Hong Kong,Japan,Singapore,Japan,South Korea,Japan,Taiwan,Japan,Denmark,Japan,France,Japan,Netherlands,Japan,Italy,Japan,Spain,Japan,Switzerland,Japan,Canada,Japan,Germany,Japan,United Kingdom,Japan,Israel,Japan
• Study type: Interventional
• Intervention(s): Selpercatinib will be administered in oral form, once daily (QD) or BID, depending upon cohort assignment.

Outcome(s)

Primary Outcome

Phase 1:
The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)

Phase 2:
ORR based on RECIST 1.1 or RANO, as appropriate to tumor type, assessed by IRC.

Secondary Outcome

Phase 1:
a.Frequency, severity, and relatedness of TEAEs and serious adverse events (SAEs)
b.Plasma concentration of selpercatinib and PK
c.ORR based on RECIST 1.1 or RANO, as appropriate to tumor type.

Phase 2:
a.Parameters of anti-tumor activity/clinical benefit, including: ORR (by Investigator), best change in tumor size from baseline (by IRC and Investigator), DOR (by IRC and Investigator), CNS ORR (by IRC), CNS DOR (by IRC), time to any and best response (by IRC and Investigator), CBR (by IRC and Investigator), PFS (by IRC and Investigator), and OS.
b.Frequency, severity and relatedness of TEAEs and SAEs
c.Plasma concentrations of selpercatinib and PK parameters,

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Phase 1 (Dose Escalation and Confirmation of the Recommended Dose in Japan):(Phase II part is currently ongoing)
1. Patients with a locally advanced or metastatic solid tumor.
2. Prior MKIs with anti-RET activity are allowed.
3. A RET gene alteration is not required initially. Once adequate PK is achieved, evidence of a RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation.
4. Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type.
5. 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.
6. Life expectancy of at least 3 months.
7. Adequate hematologic status.
8. Adequate hepatic function.
9. Adequate renal function

Phase 2 (Dose Expansion):
1. Cohorts 1 and 3: failed or intolerant to standard of care; Cohorts 2 and 4: without prior standard-first line therapy.
2. Cohorts 1-4: enrollment will be restricted to patients with evidence of a RET gene alteration in tumor (i.e., not just blood). However, a positive germline DNA test for a RET gene mutation is acceptable in the absence of tumor tissue testing for patients with MTC.
3. Cohorts 1-4: at least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate for tumor type and not previously irradiated.
4. Cohort 4: radiographic PD within the previous 14 months.
5. Cohort 6: Patients who otherwise are eligible for Cohorts 1-5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval.
6. 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, and
-cfDNA positive for a RET gene alteration not known to be present in a tumor sample.

Exclude criteria

1. Phase 2, Cohorts 1-4, an additional validated oncogenic driver that could cause resistance to selpercatinib treatment.
2. Phase 2, Cohorts 1-5: 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 2 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.

Related Information

• Primary Sponsor: Hokonohara Toshihiro
• Secondary ID(s): 2017-000800-59,NCT03157128