Elzovantinib for Solid Tumors

(SHIELD-1 Trial)

Recruiting at 52 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

95 Participants Needed

Trial Summary

What is the purpose of this trial?

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 with advanced or metastatic NSCLC, Gastric Cancer, or solid tumors harboring genetic alterations in MET. (SHIELD-I)

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.

What data supports the effectiveness of the drug Elzovantinib (TPX-0022) for solid tumors?

Research on a similar drug, Tivantinib, shows it can slow down tumor growth in certain cancers by targeting a protein called MET, which is often found in high levels in some tumors. This suggests that Elzovantinib, which may work in a similar way, could also be effective against solid tumors. ^{1 2 3 4 5}

What makes the drug Elzovantinib unique for treating solid tumors?

Elzovantinib (TPX-0022) is unique because it targets specific proteins involved in tumor growth, similar to other drugs like crizotinib, which inhibits c-Met and ALK proteins. This targeted approach can be more effective for tumors that rely on these proteins for growth, offering a potentially more precise treatment option compared to traditional chemotherapy. ^{1 3 6 7 8}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Tivantinib in hepatocellular carcinoma. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Tivantinib: a new promising mesenchymal-epithelial transition factor inhibitor in the treatment of hepatocellular carcinoma. [2013]

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

Phase 1 trial of tivantinib in combination with sorafenib in adult patients with advanced solid tumors. [2021]

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

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

5. Switzerland 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. [2023]

6. China pubmed.ncbi.nlm.nih.gov

Impact of ALK variants on brain metastasis and treatment response in advanced NSCLC patients with oncogenic ALK fusion. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases. [2022]

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

Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma. [2022]