DZD9008 vs Chemotherapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
+234 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Dizal Pharmaceuticals
Disqualifiers: Prior systemic therapy, Spinal cord compression, Concurrent EGFR mutations, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
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.
12345Is 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.
14678What 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.
134910Eligibility 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
I am 18 years old or older.
Life expectancy ≥ 12 weeks
+4 more
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.
+2 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: sunvozertinibExperimental Treatment1 Intervention
Group II: Platinum-based ChemotherapyActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
WK28 Investigative SiteMargate, FL
WK28 Investigative SiteDallas, TX
WK28 Investigative SiteTampa, FL
WK28 Investigative SitePortland, OR
More Trial Locations
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Who Is Running the Clinical Trial?
Dizal PharmaceuticalsLead Sponsor
References
Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]The novel multitargeted antimetabolite pemetrexed (Alimta), recently approved by the US Food and Drug Administration for the treatment of mesothelioma when combined with cisplatin, is also active in first- and second-line non-small-cell lung cancer (NSCLC). In a phase III trial comparing single-agent pemetrexed vs docetaxel (Taxotere) as second-line therapy in advanced NSCLC, survival was shown to be comparable between these agents, but side effects were significantly less frequent and severe for patients who received pemetrexed. In the frontline setting, phase II studies have shown significant activity and a very favorable toxicity profile of the combination of pemetrexed with a platinum agent. Pemetrexed has been well tolerated at systemic doses as a radiosensitizer when given as concurrent chest radiation, and a phase I study is under way to assess its tolerability in combination with carboplatin (Paraplatin) in this setting. Pemetrexed is an important addition to the armamentarium of medicines used to treat thoracic malignancies, and merits study in combination with other drugs having novel mechanisms of action.
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]To compare efficacy of pemetrexed versus pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer (NSCLC).
Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. [2017]Pemetrexed (Alimta) is a novel multitargeted antifolate that has activity against non-small-cell lung cancer (NSCLC). As a single agent, the response rate is 16%-23%. As second-line therapy, it has a 5% and 14% response rate with pemetrexed in NSCLC patients who have had prior cisplatin or nonplatinum chemotherapy, respectively. Pemetrexed combined with cisplatin has a response rate of 38.9%-44.8%, with a median survival of 8.9-10.9 months. Pemetrexed plus gemcitabine in NSCLC has a response rate of less than 25%. The major toxicity associated with pemetrexed is neutropenia, which may be reduced with vitamin B12 and folate nutritional supplement. Additional studies with pemetrexed in combination with other agents are needed for the treatment of NSCLC patients.
Review of a promising new agent--pemetrexed disodium. [2022]Pemetrexed disodium (ALIMTa, [pemetrexed], LY231514; Eli Lilly and Company; Indianapolis, IN), a novel antifolate antimetabolite with multiple enzyme targets involved in both pyrimidine and purine synthesis, has entered clinical trials due to its favorable pleclinical profile. Many studies utilizing the drug, as a single or combination agent, are currently ongoing, including Phase III trials in mesothelioma, nonsmall cell lung carcinoma (NSCLC) and pancreatic cancer. Promising feasibility and activity data have been obtained with pemetrexed in combination with platinum compounds and gemcitabine. The supplementation with daily oral folate could reduce the incidence of hematologic toxicities while preserving the antitumor activity of pemetrexed.
Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent. [2015]Pemetrexed (ALIMTA, LY231514, MTA) is a novel antimetabolite that inhibits at least three enzymes involved in the folate pathway. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed has demonstrated clinical activity in non-small cell lung cancer as well as in a broad array of other solid tumors, including mesothelioma, breast, colorectal, bladder, cervical, gastric and pancreatic cancer. In non-small cell lung cancer, single-agent activity has been documented in the first- and second-line settings in Phase II and Phase III trials. Promising activity has also been demonstrated when pemetrexed is combined with platinum compounds (cisplatin, carboplatin, and oxaliplatin), vinorelbine, and gemcitabine. Low level dietary supplement of folic acid and vitamin B12 has significantly decreased the mucosal and bone marrow toxicity of pemetrexed without compromising its antitumor effect.
The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. [2015]Pemetrexed (Alimta , LY231514) is a new multitargeted antifolate that inhibits several enzymes involved in the folate pathway. Pemetrexed is a potent inhibitor of thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed has demonstrated clinical activity in non-small-cell lung cancer (NSCLC) as well as in a broad array of other solid tumors including mesothelioma and breast, colorectal, bladder, cervical, gastric, and pancreatic cancer. In NSCLC, single-agent activity has been documented in the first- and second-line settings. Promising activity has also been demonstrated when pemetrexed is combined with cisplatin, vinorelbine, oxaliplatin, carboplatin, and gemcitabine. Low-level dietary supplement of folic acid and vitamin B12 has significantly improved the safety profile of pemetrexed without compromising its antitumor effect. In this review, the pharmacology and clinical activity of pemetrexed in NSCLC cancer is discussed.
FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. [2022]On August 19, 2004, pemetrexed for injection (Alimta); Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com) received accelerated approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had received prior chemotherapy. Approval was primarily based on a single, controlled, unblinded trial. Five hundred seventy-one protocol-eligible patients were randomized to receive either pemetrexed or docetaxel (Taxotere); Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharmaus.com). The primary efficacy end point was overall survival. The median survival times were 8.3 months in the pemetrexed arm and 7.9 months in the docetaxel arm. Neither superiority nor noninferiority for overall survival could be demonstrated, the latter because a reliable and consistent survival effect of docetaxel could not be estimated and because of significant crossover of pemetrexed-treated patients to docetaxel after tumor progression. Comparable response rates, 9.1% for pemetrexed and 8.8% for docetaxel, times to progressive disease, and progression-free survival times supported the conclusion that an effect of pemetrexed on survival was reasonably likely, however. In addition, pemetrexed was felt to have a more favorable safety profile than docetaxel. Of greatest importance, pemetrexed caused significantly less neutropenia, febrile neutropenia, neutropenic infections, and need for granulocyte/macrophage colony-stimulating factors.
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]Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial.
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]Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.
Genetic determinants of pemetrexed responsiveness and nonresponsiveness in non-small cell lung cancer cells. [2016]Pemetrexed disodium (Alimta), LY231514, is an antifolate that is able to simultaneously inhibit the synthesis of purines and pyrimidines. Pemetrexed has been approved for first- and second-line treatment in patients with non-small cell lung cancer (NSCLC). However, there is still a lack of clinical biomarkers for predicting the therapeutic response to pemetrexed. The aim of this study is to establish new biomarkers for pemetrexed treatment in NSCLC.