DZD9008 vs Chemotherapy for Lung Cancer

Recruiting at 234 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

320 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 3, open-label, randomized, multi-center study assessing the efficacy and safety of DZD9008 versus platinum-based doublet chemotherapy in participants with locally advanced or metastatic NSCLC with EGFR Exon20ins mutation, who are newly diagnosed or have not received prior systemic therapy in advanced stage. Primary objective of this study is to assess the efficacy of DZD9008 versus platinum-based doublet chemotherapy using by BICR-assessed PFS per RECIST 1.1 as primary endpoint. Approximately 320 participants are estimated to be randomized into the study. Participants enrolled will be randomized to DZD9008 or platinum-based doublet chemotherapy in a 1:1 manner, stratified by baseline brain metastasis (with/without).

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.

What data supports the effectiveness of the drug DZD9008 in treating lung cancer?

Pemetrexed, a component of the treatment, has shown effectiveness in treating non-small-cell lung cancer (NSCLC) both as a single agent and in combination with platinum-based drugs like carboplatin. It has demonstrated a good response rate and is generally well-tolerated, with fewer side effects compared to some other treatments. ^{1 2 3 4 5}

Is DZD9008 (Sunvozertinib) safe for humans?

Pemetrexed, a component of the chemotherapy regimen, has been shown to have a favorable safety profile with fewer severe side effects compared to other treatments like docetaxel. It is generally well-tolerated, especially when supplemented with folic acid and vitamin B12, which help reduce certain blood-related side effects. ^{1 4 6 7 8}

What makes the drug DZD9008 unique for lung cancer treatment?

DZD9008 (Sunvozertinib) is a novel treatment option for lung cancer, offering a different mechanism of action compared to traditional chemotherapy drugs like pemetrexed and carboplatin. While pemetrexed and carboplatin are established chemotherapy agents, DZD9008 represents a new approach, potentially providing an alternative for patients who may not respond well to existing treatments. ^{1 3 4 9 10}

Research Team

Caicun Zhou

Principal Investigator

Shanghai Pulmonary Hospital, Shanghai, China

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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]

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]

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 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]

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]

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 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]

References

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

Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]

2. United States 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. [2022]

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

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

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

Review of a promising new agent--pemetrexed disodium. [2022]

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

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

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

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

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

FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. [2022]

8. England 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. [2023]

9. China 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). [2023]

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

Genetic determinants of pemetrexed responsiveness and nonresponsiveness in non-small cell lung cancer cells. [2016]