DZD9008 vs Chemotherapy for Lung Cancer

Not currently recruiting at 265 trial locations

Overseen By Iris Li, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Dizal Pharmaceuticals

Disqualifiers: Prior systemic therapy, Spinal cord compression, Concurrent EGFR mutations, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DZD9008 (Sunvozertinib) for individuals with non-small cell lung cancer (NSCLC) that has a rare mutation known as EGFR Exon20ins. The study compares DZD9008 to standard chemotherapy to determine which more effectively stops the cancer from growing or spreading. Individuals recently diagnosed with this type of lung cancer who have not yet received treatment may be suitable for the trial. Participants will be randomly assigned to either the new treatment or standard chemotherapy to compare outcomes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that DZD9008, also known as sunvozertinib, is generally safe for people with non-small cell lung cancer (NSCLC) who have certain EGFR mutations. Early studies found that this treatment can effectively fight tumors and is safe for patients without previous treatment for advanced cancer. The FDA granted it accelerated approval for some lung cancer cases, indicating trust in its safety.

The trial's chemotherapy uses a mix of drugs commonly used for lung cancer. While chemotherapy can cause side effects like nausea and tiredness, its safety is well-established due to long-term use.

Overall, both treatments in this trial have evidence supporting their safety, but discussing any concerns with a healthcare provider is always best. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about DZD9008, also known as sunvozertinib, because it offers a novel approach to treating lung cancer. Unlike traditional chemotherapy, which targets rapidly dividing cells without specificity, DZD9008 is designed to target specific mutations in cancer cells, potentially leading to more effective and less toxic treatment. This precision targeting could mean fewer side effects and better outcomes for patients. Additionally, this treatment is part of a new class of drugs called tyrosine kinase inhibitors, which work by blocking signals that promote cancer cell growth, making it a promising alternative to standard chemotherapy regimens like pemetrexed combined with carboplatin.

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

Research has shown that DZD9008, also known as sunvozertinib, holds promise for treating non-small cell lung cancer (NSCLC) with a specific mutation. In earlier studies, 79% of patients who took sunvozertinib experienced tumor shrinkage and lived about 12 months without cancer progression. Sunvozertinib is generally well-tolerated, allowing most people to take it without severe side effects. In this trial, participants will receive either sunvozertinib or a platinum-based chemotherapy regimen (Pemetrexed + Carboplatin) to compare effectiveness. These findings suggest that sunvozertinib could be a strong alternative to standard chemotherapy for this type of lung cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Caicun Zhou

Principal Investigator

Shanghai Pulmonary Hospital, Shanghai, China

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-squamous Non-Small Cell Lung Cancer (NSCLC) who haven't had systemic therapy for their advanced disease. They must have a certain type of mutation in their cancer cells (EGFR Exon20ins), be able to perform daily activities with minimal assistance, and have a life expectancy of at least 12 weeks.

Inclusion Criteria

At least 1 measurable lesion per RECIST Version 1.1

Life expectancy ≥ 12 weeks

My tumor tissue can be tested for a specific genetic change.

Exclusion Criteria

I have not had a stroke or brain bleed in the last 6 months.

I do not have severe illnesses or uncontrolled high blood pressure.

I do not have cancer spread to my spinal cord or brain coverings.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either DZD9008 or platinum-based doublet chemotherapy

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DZD9008
• Pemetrexed+carboplatin

Trial Overview The study compares DZD9008, an experimental drug, against standard platinum-based chemotherapy in patients with NSCLC carrying the EGFR Exon20ins mutation. Participants will be randomly assigned to one of these treatments and monitored to see which is more effective at slowing down cancer progression.

How Is the Trial Designed?

Group I: sunvozertinib Experimental Treatment 1 Intervention

Group II: Platinum-based Chemotherapy Active Control 1 Intervention

DZD9008 is already approved in China for the following indications:

Approved in China as Sunvozertinib for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy

Who Is Running the Clinical Trial?

Dizal Pharmaceuticals

Lead Sponsor

Trials

27

Recruited

2,500+

Published Research Related to This Trial

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

Pemetrexed is an effective antimetabolite that targets key enzymes in the folate pathway and has shown clinical activity in various cancers, particularly non-small cell lung cancer, in both first- and second-line treatment settings.

Supplementing with low doses of folic acid and vitamin B12 can reduce the toxicity of pemetrexed on mucosal and bone marrow tissues while maintaining its effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent. Adjei, AA.[2015]

Pemetrexed (Alimta) shows a response rate of 16%-23% as a single agent for non-small-cell lung cancer (NSCLC) and a higher response rate of 38.9%-44.8% when combined with cisplatin, leading to a median survival of 8.9-10.9 months.

The main side effect of pemetrexed is neutropenia, but this can be mitigated with vitamin B12 and folate supplements, highlighting the importance of supportive care in enhancing treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. Ettinger, DS.[2017]

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

Pemetrexed disodium (Alimta) effectively inhibits tumor growth in non-small cell lung cancer (NSCLC) cell lines, with A549 cells showing sensitivity and H1355 cells demonstrating resistance, indicating variability in treatment response.

The study identifies potential biomarkers for predicting pemetrexed responsiveness, including downregulation of thymidylate synthase (TS) and dihydrofolate reductase (DHFR), and upregulation of lipocalin-2 (Lcn-2) and nm23-H1 in sensitive cells, which could help tailor treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic determinants of pemetrexed responsiveness and nonresponsiveness in non-small cell lung cancer cells. Wu, MF., Hsiao, YM., Huang, CF., et al.[2016]

Pemetrexed disodium is a promising new antifolate drug that targets multiple enzymes involved in the synthesis of DNA and RNA, showing potential in treating cancers like mesothelioma, non-small cell lung carcinoma, and pancreatic cancer.

Combining pemetrexed with platinum-based drugs and gemcitabine has shown encouraging results, and taking daily oral folate can help reduce side effects like blood-related toxicities while maintaining its effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of a promising new agent--pemetrexed disodium. Paz-Ares, L., Bezares, S., Tabernero, JM., et al.[2022]

In a study involving 239 patients with advanced non-small-cell lung cancer (NSCLC), the addition of carboplatin to pemetrexed did not significantly improve progression-free survival or overall survival compared to pemetrexed alone.

However, in patients with squamous cell tumors, adding carboplatin to pemetrexed showed a notable improvement in overall survival, suggesting that this combination may be beneficial for this specific subgroup and warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. Ardizzoni, A., Tiseo, M., Boni, L., et al.[2022]

Pemetrexed is a multitargeted antifolate that effectively inhibits key enzymes in the folate pathway, showing clinical activity in non-small-cell lung cancer (NSCLC) and various other solid tumors.

The addition of low-level folic acid and vitamin B12 supplements enhances the safety of pemetrexed treatment without reducing its effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Molina, JR., Adjei, AA.[2015]

Pemetrexed was approved for treating advanced non-small cell lung cancer based on a trial with 571 patients, showing median survival times of 8.3 months compared to 7.9 months for docetaxel, although neither drug was proven superior.

Pemetrexed demonstrated a better safety profile than docetaxel, causing significantly less neutropenia and related complications, making it a potentially safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. Cohen, MH., Johnson, JR., Wang, YC., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11921407/

Sunvozertinib: shining light on lung cancer's exon 20 fight Sunvozertinib monotherapy in the first-line setting demonstrated promising results with an ORR of 79% and a median PFS of 12 months for patients ...

2. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20

FDA grants accelerated approval to sunvozertinib for ... The major efficacy outcome measure was confirmed overall response rate (ORR) according to RECIST v1.1 as evaluated by a blinded independent ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00788

Phase II Dose-Randomized Study of Sunvozertinib in ... Per IRC assessment, a majority of patients had tumor size reduction of target lesions. In 200 mg-rand, 300 mg-rand, and 300 mg-all efficacy ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304383525004720

Efficacy and safety of sunvozertinib monotherapy as first- ... Sunvozertinib monotherapy demonstrated significant and durable antitumor efficacy and was well-tolerated in treatment-naïve patients with EGFR exon20ins NSCLC.

5. targetedonc.com targetedonc.com/view/sunvozertinib-proves-efficacy-in-egfr-mutant-non-small-cell-lung-cancer

Sunvozertinib Proves Efficacy in EGFR-Mutant Non-Small ... Sunvozertinib showed efficacy in NSCLC with EGFR exon 20 insertion mutations, with ORRs around 46% across dosing cohorts. Higher response rates ...

6. jto.org jto.org/article/S1556-0864(25)02627-9/fulltext

EP.12.47 Persistent Response of Sunvozertinib in Lung ... The data analyzed by investigators included response assessment by RECIST1.1 and safety outcomes. Results. A 67-year-old male patient underwent CT scan in ...