Poziotinib for Advanced Non-Small Cell Lung Cancer

Overseen By Yasir Y. Elamin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticancer treatments, Anticonvulsants, Corticosteroids

Disqualifiers: EGFR T790M mutation, Cardiac conditions, Gastrointestinal disorders, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a drug called poziotinib for individuals with advanced non-small cell lung cancer that has specific genetic changes (EGFR or HER2 exon 20 mutations). Poziotinib aims to block certain enzymes necessary for cancer cell growth, potentially slowing or stopping disease progression. This trial may suit those with stage IV cancer or recurrent cancer who have exhausted all standard treatments or cannot receive them. Participants must be able to take oral medication and have undergone genetic tests to confirm the specific mutations. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who are receiving other cancer treatments or investigational drugs. It's best to discuss your specific medications with the trial team.

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

Research has shown that poziotinib is generally safe for treating a type of lung cancer with specific mutations. Studies indicate that patients have tolerated poziotinib well, with encouraging results. In earlier trials, poziotinib provided significant benefits, even for patients who had not received prior treatment. Some patients experienced side effects, but these were usually manageable. Overall, existing data supports poziotinib's safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced non-small cell lung cancer, which often include chemotherapy and targeted therapies like EGFR inhibitors, poziotinib offers a novel approach. Poziotinib is unique because it specifically targets HER2 exon 20 mutations, a less common genetic alteration that is notoriously difficult to treat with existing options. Researchers are excited about poziotinib because it has shown potential in overcoming resistance seen in other treatments, offering new hope for patients with these specific genetic profiles. Additionally, poziotinib is administered orally, making it more convenient compared to some other treatments that require infusions.

What evidence suggests that poziotinib might be an effective treatment for advanced non-small cell lung cancer?

Previous studies have shown that poziotinib holds promise for treating non-small cell lung cancer (NSCLC) with specific genetic changes. For patients with an EGFR exon 20 mutation, poziotinib effectively shrank tumors and kept them under control for a period. Among those with a HER2 exon 20 mutation, about one in four patients experienced a noticeable reduction in tumor size. These findings suggest that poziotinib may effectively target and slow cancer cell growth in these specific genetic profiles. Although not all patients responded, these results highlight its potential as a treatment option for those with these mutations. Participants in this trial will receive poziotinib to further evaluate its effectiveness and safety in treating advanced NSCLC. ^{2 3 5 6 7}

Who Is on the Research Team?

Yasir Y. Elamin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage IV or recurrent non-small cell lung cancer (NSCLC) that has specific mutations (EGFR or HER2 exon 20). Participants must have tried all standard treatments, be able to swallow pills, and not be pregnant. They should also have adequate organ function and agree to use contraception.

Inclusion Criteria

My solid tumor, not lung cancer, has EGFR or HER2 mutations.

I have tried all standard treatments for my advanced cancer or cannot receive them.

You have a disease that can be measured using a specific medical guideline.

Exclusion Criteria

I am not using effective birth control.

I have a condition that causes me to bleed easily.

My cancer has a specific EGFR mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive poziotinib orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days and then every 6 months.

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Poziotinib

Trial Overview The trial is testing the effectiveness of Poziotinib, a drug designed to block enzymes that promote tumor growth in patients with certain genetic mutations in their lung cancer cells. It's a phase II study which means it focuses on the drug's efficacy and side effects.

How Is the Trial Designed?

Group I: Treatment (poziotinib) Experimental Treatment 1 Intervention

Patients receive poziotinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Spectrum Pharmaceuticals, Inc

Industry Sponsor

Trials

83

Recruited

8,200+

Tom Riga

Spectrum Pharmaceuticals, Inc

Chief Executive Officer since 2021

Bachelor's degree in Business Administration from the University of Rhode Island

Francois Lebel

Spectrum Pharmaceuticals, Inc

Chief Medical Officer since 2018

MD from McGill University

Published Research Related to This Trial

In a phase II study involving 30 patients with advanced HER2 exon 20 mutant non-small-cell lung cancer (NSCLC), poziotinib demonstrated a confirmed objective response rate of 27%, indicating its potential effectiveness as a targeted therapy.

The treatment was associated with a median overall survival of 15 months and a median progression-free survival of 5.5 months, although it also had notable side effects, including skin rash and diarrhea, with one possible treatment-related death from pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poziotinib for Patients With HER2 Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial. Elamin, YY., Robichaux, JP., Carter, BW., et al.[2023]

Poziotinib, a novel tyrosine kinase inhibitor, shows moderate efficacy in treating HER2 exon 20 mutant non-small-cell lung cancer (NSCLC), with an objective response rate of 27% and a disease control rate of 72% based on a pooled analysis of three clinical trials involving 126 patients.

The treatment has a manageable safety profile, with the most common severe side effects being skin rash (36%), diarrhea (23%), and oral mucositis (13%), indicating that while effective, monitoring for these adverse events is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials. Wang, BC., Kuang, BH., Liu, XX., et al.[2022]

The maximum tolerated dose (MTD) of poziotinib when combined with paclitaxel and trastuzumab for treating HER2-positive advanced gastric cancer was determined to be 8 mg/day, with manageable toxicity observed in the study.

In a cohort of 44 patients, the treatment combination showed promising efficacy, with a 21.9% objective response rate and median progression-free survival of 13 weeks, indicating potential benefits for patients previously treated with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer. Kim, TY., Han, HS., Lee, KW., et al.[2023]

Citations

1. nature.com nature.com/articles/s41467-025-61817-8

Poziotinib for EGFR exon 20-insertion NSCLC Although the study's primary efficacy endpoint was not met in the overall cohort, the exploratory analysis indicates poziotinib has superior ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8887948/

Poziotinib for Patients With HER2 Exon 20 Mutant Non– ... Poziotinib resulted in promising antitumor activity with an objective response rate of 27% in patients with advanced HER2 exon 20 mutant NSCLC. The most common ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03066206

Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC This phase II trial studies how well poziotinib works in treating patients with non-small lung cancer with an EGFR or HER2 exon 20 mutation that is stage IV ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)00060-0/fulltext

36MO Safety, tolerability and preliminary efficacy of ... Effective treatment of patients with metastatic non-small cell lung cancer ... Here we present efficacy data from once daily (QD) in treatment naïve ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT315387

Poziotinib shows activity and durability of responses in ... Poziotinib shows activity and durability of responses in subgroups of previously treated EGFR exon 20 NSCLC patients. Poziotinib shows activity and durability ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12056541/

Efficacy and safety outcomes of emerging EGFR‑TKIs for ... The emerging EGFR-TKIs for NSCLC with EGFR exon 20 insertion have a promising treatment outcome with a manageable safety profile.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34550757/

Poziotinib for Patients With HER2 Exon 20 Mutant Non-Small ... Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received ...