A Phase 1/2 Study on the effects of the LOXO-292 (study drug) in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Loxo Oncology Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 May 2020 → ongoing

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company

External identifiers

EU CT number

2023-507703-63-00

EudraCT number

2019-000212-28

WHO UTN

U1111-1302-5401

ClinicalTrials.gov

NCT03899792

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Dose response

PHASE 1
The primary objective is to determine the safety profile, including doselimiting toxicities (DLTs), of the oral RET inhibitor Selpercatinib

PHASE 2
To determine the objective response rate (ORR) as determined by an Independent Review Committee (IRC) and measured by the proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors, version 1.1(RECIST v 1.1), or Response Assessment in NeuroOncology (RANO) criteria, as appropriate, following treatment with Selpercatinib

Conditions and MedDRA coding

Pediatric Patients with Advanced RET-Altered Solid or Primary Central Nervous System Tumors

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Pediatric patients ≥ 12 years of age and ≤ 21 years of age at Cycle 1 Day 1 (C1D1) with a locally advanced or metastatic solid or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and/or for which no standard or available systemic curative therapy exists. a) Patients with locally advanced disease who would require, in the opinion of the Investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection, are also eligible. b) In geographies where a selective RET-inhibitor is approved, patients may enroll without prior systemic treatment.
2. Evidence of an activating RET gene alteration in tumor and/or blood as identified through molecular assays, as performed for clinical evaluation.
3. Patients with primary CNS tumors or cerebral metastasis: a) Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment b) Must have not required increasing doses of steroids within the 7 days prior to enrollment to manage CNS symptoms
4. Imaging study must be performed within 28 days of C1D1 while on stable dose steroid medication (if needed) for at least 7 days immediately before the imaging study.
5. Histologic verification of malignancy at original diagnosis or relapse, except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebral spinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or betahuman chorionic gonadotropin (HCG).
6. Must have measurable or non-measurable but evaluable disease.
7. Karnofsky (patients 16 years and older) or Lansky (patients younger than 16 years) performance score of at least 50.
8. Must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy to CTCAE (v5.0) Grade ≤ 2.
9. An archival (FFPE or fresh frozen) or fresh tumor tissue sample must be available (refer to Section 7.5 of the protocol).
10. Adequate hematologic/pancreatic status, defined as: a) Absolute neutrophil count (ANC) ≥ 1.0× 10^9/L not requiring growth factor support for at least 7 days prior to treatment. b) Platelet count ≥ 75 × 10^9/L not requiring transfusion support for at least 7 days prior to treatment. c) Hb ≥ 8 mg/dL not requiring transfusion support or erythropoietin for at least 7 days prior to treatment.
11. Adequate hepatic/pancreatic function, defined as: a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × the upper limit of normal (ULN) or ≤ 5 × ULN with documented liver involvement (such as liver metastasis or a primary biliary tumor), and b) Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN with documented liver involvement (patients with Gilbert's Disease may be enrolled with prior Sponsor approval)
12. Adequate renal function, defined as: a) Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 based on local institutional practice for determination, or a maximum serum creatinine by age and gender as presented in Synopsis Table 2.
13. Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
14. Willingness of male and female patients with reproductive potential to utilize double effective birth control methods
15. Ability to swallow capsules, liquid suspension, or gastric access via a naso- or gastric tube.
16. The patient and, when applicable, the parent/guardian of child or adolescent patient has the ability to understand, agree to, and sign the study Informed Consent Form (ICF) and applicable Pediatric Assent Form before initiation of any protocol-related procedures; patient has the ability to give assent, as applicable, at the time of parental/guardian consent.

Exclusion criteria 9

1. Major surgery within 2 weeks prior to C1D1
2. Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolonged QT interval corrected for heart rate (QTc) interval > 440 milliseconds for patients ≤ 15 years old and > 470 milliseconds for patients > 15 years old. For patients ≤ 15 years old, Bazett's Formula will be utilized to determine QTc. For patients > 15 years old, either method, Fridericia or Bazett's Formula may be applied.
3. Active uncontrolled systemic bacterial, viral, or fungal infection, which in the opinion of the Investigator makes the risk: benefit ratio for the patient to participate in the trial unfavorable.
4. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
5. Pregnancy or lactation.
6. Uncontrolled hypotension or hypertension ≥ Grade 3 CTCAE (v 5.0).
7. Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the patient required a modification to current thyroid medication in the 7 days before start of selpercatinib).
8. Uncontrolled symptomatic hypercalcemia or hypocalcemia.
9. Known hypersensitivity to any of the components of the investigational agent, selpercatinib or Ora-Sweet® SF and OraPlus®, for patients who will receive selpercatinib suspension.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PHASE 1 Frequency, severity and relatedness of TEAEs and SAEs, including DLTs in pediatric patients receiving selpercatinib
2. PHASE 2 ORR based on RECIST v 1.1 or RANO as appropriate to tumor type as determined by an IRC

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Loxo Oncology Inc.

Sponsor organisation

Loxo Oncology Inc.

Address

281 Tresser Boulevard Floor 9th

City

Stamford

Postcode

06901-3238

Country

United States

Scientific contact point

Organisation

Loxo Oncology Inc.

Contact name

Eli Lilly & Co.

Public contact point

Organisation

Loxo Oncology Inc.

Contact name

Eli Lilly & Co.

Third parties 7

Locations

5 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications