DK210 for Cancer

Recruiting at 6 trial locations

Overseen By DEKA Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: DEKA Biosciences

Must not be taking: Immunotherapies, Experimental therapies

Disqualifiers: Diffuse peritoneal disease, Prolonged QtC, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate safety, pharmacodynamics and biomarkers of subcutaneous (SC) DK210(EGFR) given as monotherapy and in combination with immunotherapy, chemotherapy or radiation.

Will I have to stop taking my current medications?

The trial requires that you have not received any anti-cancer medication for at least 4 weeks before starting. If you are currently on such treatments, you will need to stop them and wait for this period before participating.

What data supports the effectiveness of the drug DK210 for cancer?

Research on similar drugs, like EGFR tyrosine kinase inhibitors (TKIs), shows they are effective in treating advanced lung cancer with specific gene mutations, improving the time patients live without the disease getting worse. ^{1 2 3 4 5}

Is DK210 (EGFR) safe for humans?

Dacomitinib, a drug similar to DK210 (EGFR), has been shown to be generally safe in humans during early studies, with common side effects including mouth sores, diarrhea, and skin issues. However, it may cause increased toxicity compared to older treatments. ^{1 6 7 8 9}

Research Team

Medical Officer

Principal Investigator

DEKA Biosciences

Eligibility Criteria

This trial is for adults with advanced or metastatic tumors that are EGFR positive and have worsened despite treatment. They must have tried at least one therapy, be in good overall health with proper organ function, and not be on recent cancer treatments. Participants need measurable disease, an ECOG performance status of 0-1, a life expectancy over three months, and agree to use contraception.

Inclusion Criteria

My cancer type is known to respond to specific treatments and has high EGFR expression.

Additional criteria may apply

My cancer is worsening, shown by symptoms, tumor growth, or imaging.

Exclusion Criteria

I haven't taken any cancer treatment or experimental therapy in the last 4 weeks.

I have widespread disease in my abdomen or persistent fluid buildup.

Any other conditions that, in the investigator's opinion, might indicate the subject to be unsuitable for the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DK210 (EGFR) as monotherapy or in combination with radiation, immunotherapy, or chemotherapy. Treatment continues until unacceptable toxicity, disease progression, or withdrawal of consent.

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to be monitored for progression-free survival and overall survival

Up to 24 months

Treatment Details

Interventions

• Chemotherapy
• DK210 (EGFR)
• Immune checkpoint blockers
• Radiation therapy

Trial Overview The study tests DK210(EGFR), alone or with other therapies like immunotherapy, chemotherapy or radiation. It aims to assess safety and how the body responds to the drug by looking at certain biomarkers in patients with various types of solid tumors.

Participant Groups

Group I: DK210 (EGFR) Monotherapy (Dose escalation and expansion) Experimental Treatment 1 Intervention

DK210 (EGFR) will be administered as monotherapy three times per week via subcutaneous (SC) administration. Dose will be escalated from 0.025 mg/kg to 0.3 mg/kg or until unacceptable toxicity, disease progression, or withdrawal of consent. An expansion cohort at the optimal dose will be enrolled in parallel with the combination arms.

Group II: DK210 (EGFR) + radiation Experimental Treatment 2 Interventions

In patients with need of palliative radiation, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with short course radiation therapy (10 fractions or less) until unacceptable toxicity, disease progression, or withdrawal of consent

Group III: DK210 (EGFR) + immunotherapy Experimental Treatment 2 Interventions

In patients with good tolerance of first line immunotherapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with intravenous (IV) immune checkpoint blockers until unacceptable toxicity, disease progression, or withdrawal of consent

Group IV: DK210 (EGFR) + chemotherapy Experimental Treatment 2 Interventions

In patients with good tolerance of first line systemic therapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with second-line intravenous (IV) chemotherapy until unacceptable toxicity, disease progression, or withdrawal of consent

Who Is Running the Clinical Trial?

DEKA Biosciences

Lead Sponsor

Trials

1

Recruited

60+

Findings from Research

In a study of 11 patients with advanced non-small cell lung cancer who previously responded to gefitinib, re-treatment with a second EGFR-TKI (either gefitinib or erlotinib) resulted in a disease control rate of 73% and a median progression-free survival of 3.4 months.

The safety profile of the second EGFR-TKI treatment was acceptable, with toxicities similar to those experienced during initial gefitinib therapy, suggesting that re-treatment can be a viable option for patients who initially responded to gefitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis. Watanabe, S., Tanaka, J., Ota, T., et al.[2022]

D-0316, a third-generation EGFR tyrosine kinase inhibitor, was found to be safe and well-tolerated in a phase I trial with 84 patients, with no maximum tolerated dose reached and most adverse events being mild (grade 1 or 2).

The drug demonstrated promising efficacy, with overall response rates of 33.3% and 45.5% at doses of 50 mg and 100 mg, respectively, and a median progression-free survival of 8.3 and 9.6 months, indicating its potential as an effective treatment for patients with NSCLC harboring the EGFR T790M mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of a Third Generation EGFR Mutant-Selective Inhibitor (D-0316) in Patients with Advanced Non-Small Cell Lung Cancer. Jian, H., Wang, K., Cheng, Y., et al.[2022]

In a study of 30 patients with stage I non-small-cell lung cancer and EGFR gene mutations, treatment with EGFR tyrosine kinase inhibitors (TKIs) resulted in a high objective response rate of 76.7% and a complete disease control rate of 100%.

The median progression-free survival (PFS) was 24.5 months, with significantly longer PFS in patients treated with icotinib compared to gefitinib (30.5 months vs 12.0 months), indicating that EGFR-TKIs are an effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line EGFR-TKIs Treatment in Stage I Non-Small-Cell Lung Cancer Patients Harboring EGFR Gene Mutations with Postoperative Intrapulmonary Recurrence. Zhu, Z., Chai, Y.[2022]

In a randomized phase II study involving 46 patients with advanced EGFR-mutated non-small cell lung cancer, continuing erlotinib therapy beyond disease progression did not improve progression-free survival compared to chemotherapy alone, with median PFS of 4.4 months for the combination versus 5.5 months for chemotherapy alone.

The study found that patients receiving erlotinib alongside chemotherapy experienced significantly more toxicity without any added therapeutic benefit, suggesting that continuing erlotinib after progression is not advisable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib-Responsive Non-Small Cell Lung Cancer. Halmos, B., Pennell, NA., Fu, P., et al.[2018]

In a clinical trial involving 20 patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC), SH-1028 demonstrated manageable safety and promising antitumor activity, particularly at a dose of 200 mg once daily.

The overall objective response rate (ORR) was 40%, with a notable 75% ORR in the 200 mg cohort, indicating that SH-1028 could be an effective treatment option for patients who have progressed after previous EGFR TKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of SH-1028 in EGFR T790M-positive advanced non-small cell lung cancer patients: A dose-escalation phase 1 study. He, J., Ma, P., Zhao, D., et al.[2023]

Dacomitinib is a second-generation irreversible HER tyrosine kinase inhibitor that has shown anti-tumor activity against lung cancer, including cases with resistant EGFR mutations like T790, based on preclinical studies.

In clinical trials, dacomitinib was well tolerated at a maximum dose of 45 mg/day, with manageable side effects such as stomatitis, diarrhea, and skin toxicities, demonstrating its potential effectiveness in treating both naive and resistant HER tyrosine kinase settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dacomitinib for the treatment of advanced or metastatic non-small-cell lung cancer. Mok, T., Lee, K., Tang, M., et al.[2019]

In a phase III trial, the irreversible EGFR inhibitor dacomitinib was found to be more effective than the first-generation EGFR inhibitor gefitinib in reducing lung cancer progression.

However, dacomitinib also increased toxicity levels, which may restrict its use compared to newer, safer, and more effective third-generation EGFR inhibitors that are in development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dacomitinib Beats Gefitinib for EGFR+ NSCLC. [2019]

Gefitinib is an effective treatment for patients with advanced non-small-cell lung cancer who have not responded to previous chemotherapy, showing a high response rate of 93% when used as a second- or third-line therapy.

While gefitinib improves quality of life and pulmonary symptoms, it does not provide additional survival benefits when combined with standard chemotherapy, and it carries risks of adverse effects, including severe interstitial lung disease in about 1% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefitinib: a new antineoplastic for advanced non-small-cell lung cancer. Cersosimo, RJ.[2019]

In a pooled analysis of 21 clinical trials involving 1468 patients with EGFR mutation-positive non-small cell lung cancer, afatinib was found to cause significantly more severe adverse events, such as rash and diarrhea, compared to erlotinib and gefitinib.

Gefitinib was associated with a higher frequency of severe hepatotoxicity compared to the other two drugs, while the overall rates of severe interstitial lung disease were low and similar across all three EGFR-TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Takeda, M., Okamoto, I., Nakagawa, K.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Phase I Trial of a Third Generation EGFR Mutant-Selective Inhibitor (D-0316) in Patients with Advanced Non-Small Cell Lung Cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

First-Line EGFR-TKIs Treatment in Stage I Non-Small-Cell Lung Cancer Patients Harboring EGFR Gene Mutations with Postoperative Intrapulmonary Recurrence. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib-Responsive Non-Small Cell Lung Cancer. [2018]

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

Safety, efficacy, and pharmacokinetics of SH-1028 in EGFR T790M-positive advanced non-small cell lung cancer patients: A dose-escalation phase 1 study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Dacomitinib for the treatment of advanced or metastatic non-small-cell lung cancer. [2019]

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

Dacomitinib Beats Gefitinib for EGFR+ NSCLC. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Gefitinib: a new antineoplastic for advanced non-small-cell lung cancer. [2019]

9. Ireland pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. [2022]