Zipalertinib + Chemotherapy for Non-Small Cell Lung Cancer

Overseen By Tina Tieu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Antineoplastics, Corticosteroids

Disqualifiers: Immunodeficiency, Pneumonitis, Hepatitis, 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: 23

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new drug, zipalertinib, combined with standard chemotherapy drugs, carboplatin and pemetrexed, in treating certain types of surgically removable non-small cell lung cancer (NSCLC). The goal is to determine if this combination can halt cancer cell growth more effectively than current treatments. This trial suits individuals with stage II-IIIB non-small cell lung cancer who have not yet received systemic therapy and have specific gene mutations in their cancer cells. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received any antineoplastic therapy (cancer treatment) within 30 days before starting the trial. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown zipalertinib to be generally safe. Most patients tolerated the treatment well, with only a few needing to adjust their dose or discontinue due to side effects. The low rate of treatment changes or discontinuations indicates good safety.

Carboplatin and pemetrexed, the other two drugs in this trial, are already used to treat cancer. Carboplatin is considered gentler on the body compared to a similar drug, cisplatin. Pemetrexed works by stopping cancer cells from growing. Both drugs are usually well-tolerated, though, like all cancer treatments, they can cause side effects.

Overall, studies have shown that the combination of treatments in this trial is safe. However, individual reactions to the treatment may vary. Discuss any concerns with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about zipalertinib combined with carboplatin and pemetrexed for non-small cell lung cancer because it introduces a new active ingredient, zipalertinib, which may offer enhanced effectiveness. Unlike standard treatments, which often rely solely on chemotherapy drugs like carboplatin and pemetrexed, this combination includes zipalertinib, a novel agent that could enhance the overall anti-cancer effect. Additionally, zipalertinib is administered orally, which can offer more convenience compared to traditional intravenous chemotherapy. The combination aims to improve outcomes by potentially reducing cancer progression more effectively than existing treatments.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will evaluate the combination of zipalertinib with carboplatin and pemetrexed for treating non-small cell lung cancer (NSCLC). Studies have shown that zipalertinib effectively treats NSCLC by blocking certain enzymes that promote cancer cell growth, potentially stopping or slowing the cancer. Earlier research indicated that patients with specific changes in their cancer cells experienced promising results with zipalertinib, suggesting it as a strong treatment for this type of lung cancer. When combined with carboplatin and pemetrexed, well-known cancer drugs, zipalertinib might enhance the destruction of cancer cells. These findings suggest the treatment could be effective for patients with resectable stage II-IIIB NSCLC. ^{1 2 3 4 6}

Who Is on the Research Team?

Arjan Gower, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with stage II-IIIB non-small cell lung cancer that can be surgically removed. Participants must meet certain health criteria to join, but specific inclusion and exclusion details are not provided.

Inclusion Criteria

ANC ≥ 1.0 x 10^9/L

Hemoglobin ≥ 9 g/dL without transfusion or EPO dependency

My kidney function is good.

Exclusion Criteria

I have a history of seizures that are not controlled.

History of allogeneic organ transplant

I have HIV but am on treatment and my viral load is undetectable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Treatment

Participants receive zipalertinib orally twice daily, and carboplatin and pemetrexed intravenously on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles.

12 weeks

4 visits (in-person)

Surgery

Participants undergo standard of care resection surgery within 30 days after neoadjuvant treatment.

1 week

1 visit (in-person)

Adjuvant Treatment

Between 4 and 12 weeks after surgery, participants receive zipalertinib orally twice daily for 13 cycles, each cycle lasting 21 days.

39 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits every 12 weeks for up to 1 year.

52 weeks

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Pemetrexed
• Zipalertinib

Trial Overview The study is testing the effectiveness of zipalertinib combined with carboplatin and pemetrexed in treating early-stage lung cancer before surgery. It explores how well these drugs work together to stop tumor growth by blocking enzymes and destroying tumor cells.

How Is the Trial Designed?

Group I: Treatment (Zipalertinib, carboplatin, pemetrexed) Experimental Treatment 7 Interventions

NEOADJUVANT: Patients receive zipalertinib PO BID on days 1-21, and carboplatin IV, over 15-60 minutes, and pemetrexed IV, over 10 minutes, on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Within 30 days patients undergo standard of care resection surgery. ADJUVANT: Between 4 and 12 weeks after surgery patients receive zipalertinib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT scan and/or MRI during screening and CT scan and blood and urine sample collection throughout the study.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Taiho Oncology, Inc.

Industry Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Citations

1. taihooncology.com taihooncology.com/us/news/taiho-oncology-and-cullinan-therapeutics-present-data-on-zipalertinib-at-the-iaslc-2025-world-conference-on-lung-cancer/

Taiho Oncology and Cullinan Therapeutics Present Data ... Updated efficacy and safety data to be presented from the REZILIENT1 trial of zipalertinib from the cohort of patients with non-small cell ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00763

Zipalertinib in Patients With Epidermal Growth Factor ... Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40450572/

Zipalertinib in Patients With Epidermal Growth Factor ... Conclusion: Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC ...

4. onclive.com onclive.com/view/zipalertinib-shows-early-efficacy-with-manageable-safety-in-egfr-mutant-nsclc-with-cns-or-leptomeningeal-disease

Zipalertinib Shows Early Efficacy With Manageable Safety ... Zipalertinib demonstrated preliminary efficacy and low rates of treatment-related dose reductions and discontinuations in NSCLC harboring EGFR ...

5. prnewswire.com prnewswire.com/news-releases/taiho-oncology-and-cullinan-therapeutics-present-data-on-zipalertinib-at-the-iaslc-2025-world-conference-on-lung-cancer-302549926.html

Taiho Oncology and Cullinan Therapeutics Present Data ... Updated efficacy and safety data to be presented from the REZILIENT1 trial of zipalertinib from the cohort of patients with non-small cell ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04759-8/fulltext

670P Phase III study of zipalertinib plus first-line (1L) ... Zipalertinib, a novel, covalently binding oral EGFR tyrosine kinase inhibitor, demonstrated encouraging antitumor activity as a monotherapy in the phase I/2 ...