Selpercatinib for Solid Tumors

(LIBRETTO-001 Trial)

Not currently recruiting at 120 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, LOXO-292 (also known as Selpercatinib), to determine its safety and effectiveness in treating various advanced solid tumors, including certain thyroid cancers and tumors with a specific gene change called RET. The study aims to understand how the drug functions in the body and its ability to shrink tumors. Individuals with a solid tumor that has worsened despite other treatments, or for whom standard treatments are unsuitable, might be suitable candidates. Participants should have a measurable tumor or cancer that can be monitored.

As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

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 there any evidence suggesting that selpercatinib is likely to be safe for humans?

Research has shown that selpercatinib, also known as LOXO-292, is generally well-tolerated by people with advanced solid tumors. One study found that patients taking selpercatinib experienced manageable side effects. Many patients continued the treatment safely with some dose adjustments.

Long-term treatment with selpercatinib is feasible, and adjusting the dose can manage unwanted side effects. This allows most patients to continue the treatment without major issues.

Additionally, the FDA has approved selpercatinib for treating certain cancers, indicating a safety record that meets regulatory standards for those conditions. However, individual experiences with the medication can vary. Patients should always discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Selpercatinib, also known as LOXO-292, is unique because it targets a specific genetic abnormality in certain solid tumors, specifically those involving RET gene fusions or mutations. Unlike many conventional chemotherapy treatments that attack rapidly dividing cells indiscriminately, selpercatinib precisely blocks the activity of the altered RET protein, potentially leading to more effective treatment with fewer side effects. Researchers are excited because this targeted approach could offer new hope for patients whose tumors harbor these genetic changes, and it may work even when other treatments have failed.

What evidence suggests that selpercatinib might be an effective treatment for solid tumors?

Studies have shown that selpercatinib effectively treats certain cancers with specific genetic changes. In patients with RET fusion-positive solid tumors, about 44% experienced significant tumor shrinkage, with some achieving complete tumor disappearance. For those with cancer that had spread to the brain, the response rate reached 85%. Selpercatinib also demonstrates long-lasting effects and is generally well-tolerated by patients with these cancer types. Overall, research suggests that selpercatinib could be a promising option for treating these challenging cancers.

In this trial, participants will receive multiple doses of selpercatinib to determine the maximum tolerated dose and recommended Phase 2 dose, further exploring its potential benefits. ^{2 6 7 8 9}

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 are expected to live for at least 3 more months.

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 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™) 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 (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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10524590/

FDA Approval Summary: Selpercatinib for the treatment of ... Table 2: Efficacy Results in Patients with RET Fusion-Positive Solid Tumors in Study LIBRETTO-001. ; Complete response, 4.9% ; Partial response, 39% ; Duration of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12378005/

Selpercatinib for RET fusion-positive non-small cell lung cancer In 26 patients with measurable brain metastases at baseline, the response rate was 85% (complete response rate 27%) and median duration of ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.746

Durable efficacy of selpercatinib in patients with RET ... Conclusions: Selpercatinib continued to demonstrate durable antitumor activity and tolerable safety in pts with RET fusion+ cancers across ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03157128?cond=RET%20Cancer&country=United%20States&locStr=United%20States&viewType=Table&rank=5

A Study of Selpercatinib (LOXO-292) in Participants With ... This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309719

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant ... Selpercatinib treatment resulted in superior progression-free survival and treatment failure–free survival as compared with cabozantinib or vandetanib in ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/213246s008lbl.pdf

Retevmo - accessdata.fda.gov The pharmacokinetics of selpercatinib were evaluated in patients with locally advanced or metastatic solid tumors administered 160 mg twice daily unless ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03157128

NCT03157128 | A Study of Selpercatinib (LOXO-292) in ... This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of ...

8. academic.oup.com academic.oup.com/oncolo/article/29/12/1068/7849621

Long-term safety of selpercatinib for Rearranged during ... Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.

9. mayoclinic.org mayoclinic.org/drugs-supplements/selpercatinib-oral-route/description/drg-20489652

Selpercatinib (oral route) - Side effects & dosage Safety and efficacy have not been established. Appropriate studies performed to date have not demonstrated pediatric-specific problems that ...