DZD6008 for Lung Cancer

Overseen By Mengzhu Zhang

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dizal Pharmaceuticals

Must not be taking: Immunotherapy, Anticancer drugs, Proton pump inhibitors, others

Disqualifiers: Uncommon EGFR mutations, SCLC, Uncontrolled hypertension, Active infection, others

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

Compensation: Varies

Number of Visits: 18

48 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications before joining the trial. Specifically, if you are taking drugs that affect the enzyme CYP3A4 or proton pump inhibitors, you will need to stop them for a period of time before starting the study drug. Please discuss your current medications with the study team to see if any changes are needed.

What data supports the effectiveness of the drug DZD6008 for lung cancer?

The drug sunvozertinib (DZD9008), which is similar to DZD6008, has shown promising results in treating non-small cell lung cancer with specific mutations. It demonstrated strong antitumor activity in both lab studies and early clinical trials, with patients experiencing positive responses at certain doses. ^{1 2 3 4 5}

What safety data exists for DZD6008 (also known as sunvozertinib) in humans?

Sunvozertinib (DZD9008) was generally well-tolerated in phase I clinical studies up to a dose of 400 mg once daily. The most common side effects were diarrhea and skin rash. ^{1 3 6 7 8}

What is the purpose of this trial?

This study is designed to evaluate safety and anti-tumor activity of DZD6008 in patients with advanced NSCLC with EGFR mutations.

Eligibility Criteria

This trial is for patients with advanced non-small cell lung cancer (NSCLC) who have specific EGFR mutations. Detailed eligibility criteria are not provided, but typically participants would need to meet certain health standards and mutation profiles.

Inclusion Criteria

I am mostly active and my doctor expects me to live 12 weeks or more.

My brain metastases are stable.

My blood counts and organ functions are within normal ranges.

Exclusion Criteria

I have or had interstitial lung disease.

I do not have any conditions that affect how my body absorbs medication.

I have not received a live vaccine in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Dose Escalation

Locally advanced or metastatic NSCLC patients with EGFR sensitizing mutations receive escalating doses of DZD6008

21 weeks

7 cycles, each cycle is 21 days

Part B: Dose Expansion

Patients with EGFR sensitizing mutations and C797X mutation receive selected doses of DZD6008

33 weeks

11 cycles, each cycle is 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• DZD6008

Trial Overview The study focuses on the safety and effectiveness of DZD6008, an oral medication targeting the EGFR pathway in NSCLC. It's likely a phase trial where dosage and response are closely monitored.

Participant Groups

Group I: Experimental: Part B Dose Expansion cohorts (selected dose 2 QD) Experimental Treatment 1 Intervention

Group II: Experimental: Part B Dose Expansion cohorts (selected dose 1 QD) Experimental Treatment 1 Intervention

Group III: Experimental: Part A Dose Escalation cohorts (90 mg QD) Experimental Treatment 1 Intervention

Group IV: Experimental: Part A Dose Escalation cohorts (60 mg QD) Experimental Treatment 1 Intervention

Group V: Experimental: Part A Dose Escalation cohorts (40 mg QD) Experimental Treatment 1 Intervention

Group VI: Experimental: Part A Dose Escalation cohorts (20 mg once daily [QD]) Experimental Treatment 1 Intervention

Group VII: Experimental: Part A Dose Escalation cohorts (150 mg QD) Experimental Treatment 1 Intervention

Group VIII: Experimental: Part A Dose Escalation cohorts (120 mg QD) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Dizal Pharmaceuticals

Lead Sponsor

Trials

27

Recruited

2,500+

Findings from Research

The combination of mocetinostat (70 mg TIW) and durvalumab was generally well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with an objective response rate (ORR) of 11.5% across all phase II cohorts, indicating some effectiveness in this challenging population.

Notably, the treatment showed a higher ORR of 23.1% in patients whose disease was refractory to prior checkpoint inhibitor therapies, suggesting that mocetinostat may help overcome resistance to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study. Johnson, ML., Strauss, J., Patel, MR., et al.[2023]

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]

References

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

Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. [2022]

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

Heterogeneity and Coexistence of T790M and T790 Wild-Type Resistant Subclones Drive Mixed Response to Third-Generation Epidermal Growth Factor Receptor Inhibitors in Lung Cancer. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR-Tyrosine Kinase Inhibitors. [2019]

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

Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study. [2023]

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

Poziotinib Shows Promise for Rare Lung Cancer. [2019]

6. Singapore pubmed.ncbi.nlm.nih.gov

Anlotinib plus chemotherapy for T790M-negative EGFR-mutant non-sqNSCLC resistant to TKIs: A multicenter phase 1b/2 trial. [2023]

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

Poziotinib for Patients With HER2 Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Exceptional Response to Poziotinib in Patient with Metastatic Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutation. [2022]