Elzovantinib for Solid Tumors

(SHIELD-1 Trial)

Not currently recruiting at 57 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Turning Point Therapeutics, Inc.

Must not be taking: Anti-arrhythmics, QT prolonging drugs

Disqualifiers: Other malignancies, Cardiovascular disease, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TPX-0022 (Elzovantinib) to determine its safety and effectiveness for individuals with certain advanced cancers, such as lung cancer (NSCLC) or stomach cancer, that involve specific genetic changes in the MET gene. The study aims to assess the treatment's efficacy, how the body processes it, and any potential side effects. Individuals diagnosed with these cancers and a MET gene alteration may be suitable candidates for this study. Participants should have conditions that are not treatable with surgery or other standard treatments. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications that affect heart rhythm, you might need to discuss this with the trial team, as certain heart conditions and medications are part of the exclusion criteria.

Is there any evidence suggesting that TPX-0022 is likely to be safe for humans?

Research has shown that elzovantinib (also called TPX-0022) is being tested for safety in people with various advanced cancers, such as lung and stomach cancer. In earlier studies, most patients tolerated the treatment well. The side effects were usually mild to moderate, including tiredness or nausea, which are common with many cancer treatments.

The current research remains in the early stages, aiming to determine the right dose and ensure safety. As this is a new treatment, scientists are closely monitoring for any unexpected side effects. Prospective trial participants should discuss with the research team to gain more information about what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about elzovantinib because, unlike most treatments for solid tumors, which often focus on generalized chemotherapy or radiation, elzovantinib targets specific genetic alterations in tumors. This drug is designed to inhibit the MET signaling pathway, which is implicated in certain types of cancer like non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations and MET-amplified gastrointestinal cancers. By focusing on these genetic markers, elzovantinib offers a more personalized approach, potentially improving effectiveness and reducing side effects compared to standard therapies.

What evidence suggests that TPX-0022 might be an effective treatment for solid tumors?

Research has shown that elzovantinib (TPX-0022), the investigational treatment in this trial, may help treat certain advanced cancers, particularly those with specific changes in the MET gene. In previous studies, patients with non-small cell lung cancer (NSCLC) and other solid tumors with MET gene changes received this treatment. Early results indicated that many patients experienced tumor reduction. Specifically, some NSCLC patients who had not previously tried MET-targeted therapy showed positive responses. Overall, elzovantinib appears effective against tumors with these genetic changes, offering hope for patients with hard-to-treat cancers. ^{1 2 5 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Adults over 18 with advanced or metastatic lung (NSCLC), stomach cancer, or solid tumors with specific genetic changes in MET. They must have a good performance status, measurable disease, and adequate organ function. Not for those with certain heart conditions, other recent cancers, severe infections, significant neuropathy or who are candidates for curative surgery/radiotherapy.

Inclusion Criteria

My cancer has a specific MET mutation or amplification.

I am fully active and can carry on all pre-disease activities without restriction.

Life expectancy ≥ 12 weeks

Exclusion Criteria

I have moderate to severe numbness, pain, or weakness in my hands or feet.

My liver function is better than or equal to Child-Pugh Class A.

My heart may not be functioning properly, or I have a history of heart issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluate the overall safety profile, single and multiple dose PK profiles, and preliminary efficacy of TPX-0022 in adults with advanced solid tumors harboring genetic alterations in MET

Approximately 4 weeks

Dose Expansion

Evaluate the preliminary efficacy and overall safety profile of TPX-0022 at the RP2D in defined cohorts of adult subjects in NSCLC, Gastric Cancer, and advanced solid tumors

Approximately 48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TPX-0022

Trial Overview

The trial is testing TPX-0022 (elzovantinib), a new drug targeting MET/CSF1R/SRC proteins in tumors. It's an early-stage study to check safety and how well it works against different types of advanced cancers that have alterations in the MET gene.

How Is the Trial Designed?

Group I: Phase 1 elzovantinib Experimental Treatment 1 Intervention

The dose-escalation part of the study will determine the safety, tolerability, MTD, and RP2D of elzovantinib. The dose-expansion part of the study will determine the safety, tolerability, PK, and preliminary efficacy in specific cohorts. Dose expansion cohorts: Cohort I (NSCLC, METΔex14, treatment Naive) Enrollment Closed; Cohort II (NSCLC with METΔex14, MET therapy pre-treated) Enrollment closed; Cohort III (MET amplified NSCLC, GCN≥10); Cohort IV (MET amplified GI cancer GC/GEJ, CRC/HCC, GCN≥10); Cohort V (NSCLC or GI MET amplified, GCN≥5 and \< 10); Cohort VI (Solid tumors with MET fusions, or oncogenic MET mutations or MET amplified other than GI/NSCLC

Who Is Running the Clinical Trial?

Turning Point Therapeutics, Inc.

Lead Sponsor

Trials

10

Recruited

790+

Published Research Related to This Trial

Tivantinib is an oral medication that selectively inhibits the MET protein, showing significant anti-tumor activity, particularly in patients with high MET expression, as demonstrated in a Phase II study for hepatocellular carcinoma.

The Phase II study revealed that tivantinib significantly improved time to progression compared to placebo, especially in MET-high patients, while the most common side effects were hematologic events, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tivantinib: a new promising mesenchymal-epithelial transition factor inhibitor in the treatment of hepatocellular carcinoma. Rimassa, L., Personeni, N., Simonelli, M., et al.[2013]

Amivantamab-vmjw has shown a 40% overall response rate in patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, based on a phase 1 trial involving 81 participants, indicating its efficacy after platinum-based chemotherapy.

The treatment resulted in a median progression-free survival of 8.3 months and an overall survival of 22.8 months, with an acceptable safety profile, marking it as a significant advancement for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. Shah, V., McNatty, A., Simpson, L., et al.[2023]

The combination of tivantinib and sorafenib was found to be safe and tolerable in 87 patients with advanced solid tumors, with the most common side effects being rash, diarrhea, and anorexia, but no unexpected toxicities were reported.

Preliminary results showed a 12% overall response rate, with higher efficacy in specific cancers: 26% in melanoma, 15% in renal cell carcinoma, and 10% in hepatocellular carcinoma, indicating potential therapeutic benefits for these tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of tivantinib in combination with sorafenib in adult patients with advanced solid tumors. Puzanov, I., Sosman, J., Santoro, A., et al.[2021]

Cabozantinib and temozolomide both significantly reduced the growth and viability of uterine sarcoma cells, with the combination of the two drugs showing even greater effectiveness in promoting cell death and inhibiting tumor growth.

In mouse models, the combined treatment of cabozantinib and temozolomide led to a significant reduction in tumor size, indicating a synergistic effect that supports further clinical trials for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma. Noh, JJ., Cho, YJ., Ryu, JY., et al.[2022]

The combination of the PD-L1 inhibitor atezolizumab with standard chemotherapy significantly improves overall survival in patients with metastatic triple-negative breast cancer compared to chemotherapy alone.

This research suggests that adding atezolizumab could provide a new treatment option for patients suffering from this aggressive form of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitor Improves Survival in TNBC. [2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03993873

NCT03993873 | Study of TPX-0022 in Patients With ...

A phase 1/2, first-in-human, open-label study of the safety, tolerability, PK, and efficacy of the novel MET/CSF1R/SRC inhibitor TPX-0022 in adult subjects ...

2.

aacrjournals.org

aacrjournals.org/mct/article/20/12_Supplement/P225/676110/Abstract-P225-Preliminary-interim-data-of

Abstract P225: Preliminary interim data of elzovantinib (TPX ...

Results: As of 13 May 2021, 52 patients have been enrolled across 7 dose levels, including 30 NSCLC patients (20 Δex14, 8 amplifications, 2 ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10708960/

Structural insight into the macrocyclic inhibitor TPX-0022 of c ...

An ongoing phase I/II study (NCT03993873) will evaluate the safety, tolerability, pharmacokinetics and efficacy of TPX-0022 for patients with ...

4.

ejcancer.com

ejcancer.com/article/S0959-8049(22)00992-3/pdf

Preliminary interim data of elzovantinib (TPX- ...

Results: As of 13 May 2022, 59 pts have been enrolled across 8 dose levels in the dose-escalation phase, including 33 NSCLC pts (21 Δex14, 9 amplifications, 3 ...

5.

clin.larvol.com

clin.larvol.com/trial-detail/NCT03993873

Study of TPX-0022 in Patients With Advanced NSCLC, ...

TPX-0022 was generally well tolerated, with the most frequent treatment emergent adverse event (TEAE) being Grade 1 or 2 dizziness; Of 10 MET TKI-naïve patients ...

6.

ejcancer.com

ejcancer.com/article/S0959-8049(22)00992-3/abstract

Preliminary interim data of elzovantinib (TPX-0022), a ...

The Phase 1 SHIELD-1 trial (NCT03993873) is evaluating safety, pharmacokinetics (PK), and preliminary activity of elzovantinib in patients (pts) with advanced ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS3663

A phase I, open-label, multicenter, first-in-human study of ...

Methods: This is a multicenter phase 1 first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of ...