Selpercatinib for Solid Tumors

(LIBRETTO-001 Trial)

Recruiting at 108 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eli Lilly and Company

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Oncogenic driver, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

857 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new oral drug called selpercatinib in patients with advanced cancers that have specific gene changes. The drug aims to block a gene that helps cancer grow, potentially slowing or stopping the disease.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot take certain strong medications that affect liver enzymes (CYP3A4 inhibitors or inducers) and other prohibited medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is Selpercatinib safe for humans?

Selpercatinib has been shown to have a manageable safety profile in clinical trials, with common side effects including high blood pressure, elevated liver enzymes, swelling, diarrhea, fatigue, dry mouth, abdominal pain, constipation, rash, nausea, and headache. Most side effects can be managed with dose adjustments, and only a small number of patients stopped treatment due to side effects. ^{1 2 3 4 5}

What makes the drug Selpercatinib unique for treating solid tumors?

Selpercatinib is unique because it is a highly selective inhibitor that targets RET (rearranged during transfection) alterations, which are specific genetic changes found in some cancers. It is effective in treating RET fusion-positive cancers, including non-small cell lung cancer and thyroid cancer, and can be taken orally, making it convenient for patients. ^{1 2 6 7 8}

What data supports the effectiveness of the drug Selpercatinib for solid tumors?

Selpercatinib has shown effectiveness in treating various advanced solid tumors with RET gene fusions, achieving a 44% response rate in a clinical trial. It is already approved for certain lung and thyroid cancers, indicating its potential in treating other solid tumors. ^{1 2 3 4 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for people with advanced solid tumors, RET fusion-positive solid tumors, or medullary thyroid cancer who have tried standard treatments without success or can't tolerate them. They must have a life expectancy of at least 3 months and good organ function. People with certain genetic alterations may join only after Sponsor approval. Those who've had recent major surgery, other cancer therapies, or untreated brain metastases are excluded.

Inclusion Criteria

My lung cancer is in an early stage, operable, and has not been treated yet.

My cancer does not initially need a RET gene alteration, but will require it after initial treatment.

You have a disease that can be measured by specific guidelines for your type of tumor.

Exclusion Criteria

I have not had major surgery in the last 2 weeks.

I am not taking strong drugs that affect liver enzymes or forbidden medications.

I don't have severe side effects from past treatments, except for hair loss or mild nerve pain from platinum-based therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Participants receive multiple doses of LOXO-292 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)

28 days

Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)

Phase 2: Dose Expansion

Participants receive the recommended phase 2 dose (RP2D) of LOXO-292 to evaluate safety, tolerability, and preliminary anti-tumor activity

12 months

Approximately every 8 weeks for one year, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 12 weeks, 7 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• LOXO-292

Trial Overview The study tests Selpercatinib (LOXO-292), an oral medication targeting specific genetic changes in tumors. It's given to participants with various types of advanced cancers to assess its safety and how well it works against these cancers.

How Is the Trial Designed?

Group I: LOXO-292 Experimental Treatment 1 Intervention

Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)

LOXO-292 is already approved in United States for the following indications:

Approved in United States as Retevmo for:

• Non-small cell lung cancer (NSCLC) with RET fusion
• Medullary thyroid cancer (MTC) with RET mutation
• Thyroid cancer with RET fusion

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Loxo Oncology, Inc.

Industry Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Published Research Related to This Trial

Selpercatinib showed a high objective response rate (ORR) of 84% in treatment-naive patients and 61% in those previously treated with platinum-based chemotherapy, indicating its efficacy in RET fusion-positive non-small-cell lung cancer (NSCLC).

The treatment demonstrated durable responses, with a median duration of response (DoR) of 20.2 months for treatment-naive patients and 28.6 months for those pretreated, along with a significant intracranial ORR of 85% in patients with CNS metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. Drilon, A., Subbiah, V., Gautschi, O., et al.[2023]

In a randomized phase 3 trial involving 212 patients, selpercatinib demonstrated a significantly longer median progression-free survival of 24.8 months compared to 11.2 months for platinum-based chemotherapy, indicating its superior efficacy in treating advanced RET fusion-positive non-small-cell lung cancer (NSCLC).

Selpercatinib also showed a higher objective response rate of 84% compared to 65% for the control treatment, and it was particularly effective in delaying disease progression in the central nervous system, with a hazard ratio of 0.28.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. Zhou, C., Solomon, B., Loong, HH., et al.[2023]

Selpercatinib (RETEVMO™) is a targeted therapy that inhibits the RET receptor tyrosine kinase, specifically designed for cancers with RET alterations.

It received FDA approval based on the promising results from the phase I/II LIBRETTO-001 trial for treating RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer, and RET-mutant medullary thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib: First Approval. Markham, A.[2021]

Selpercatinib is an effective oral treatment for advanced RET fusion-positive non-small cell lung cancer (NSCLC), showing strong and lasting responses in both previously treated and treatment-naïve patients during a pivotal phase 1/2 clinical trial.

The drug has a manageable safety profile, with most adverse events being manageable through dose adjustments, and only a small number of patients discontinuing treatment due to side effects, which primarily included hypertension and elevated liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC. Nie, T., Syed, YY.[2023]

Selpercatinib (Retevmo) received accelerated FDA approval for treating adult patients with advanced solid tumors that have RET gene fusions, showing a 44% overall response rate in a study of 41 patients with various tumor types.

The treatment demonstrated a median duration of response of 24.5 months, indicating its potential long-term efficacy, while common side effects included edema, diarrhea, and fatigue, affecting over 25% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. Duke, ES., Bradford, D., Marcovitz, M., et al.[2023]

In a study of 329 patients with RET fusion-positive NSCLC, 7% experienced hypersensitivity reactions to selpercatinib, with a higher incidence in patients previously treated with immune checkpoint inhibitors (ICIs) (77% of cases).

Hypersensitivity reactions to selpercatinib were manageable with supportive care, and many patients were able to continue treatment after dose modifications, indicating that while there is a risk, it is generally low and reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001. McCoach, CE., Rolfo, C., Drilon, A., et al.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Selpercatinib: First Approval. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety Analysis of Selpercatinib in Patients with RET Fusion-Positive Non-Small Cell Lung Cancer-Results from the Japanese Subset of a Global Phase 1/2 Study]. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib. [2021]