H002 for Non-Small Cell Lung Cancer

Recruiting at 3 trial locations

Overseen By Anna Chen

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: RedCloud Bio

Must be taking: EGFR-TKI

Must not be taking: Immunotherapy, Biotherapy, Chemotherapy, others

Disqualifiers: EGFR exon 20, Brain metastases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase I/IIa, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK and preliminary anti-tumor activity of H002 when given orally in patients with active EGFR mutation locally advanced or metastatic non-small cell lung cancer (NSCLC). The study will contain two parts: Part A is dose escalation phase (i.e., Phase I) and Part B is dose expansion phase (i.e., Phase IIa).

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

The trial requires stopping certain medications before starting H002. You must stop EGFR-TKIs 8 days before, immunotherapy or biotherapy 4 weeks before, and certain other drugs like strong CYP3A4 inhibitors 2 weeks before. The protocol does not specify all medications, so consult your doctor for guidance.

What data supports the idea that H002 for Non-Small Cell Lung Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of H002 for Non-Small Cell Lung Cancer. The studies mentioned focus on other treatments and factors related to this type of cancer, such as high-dose cisplatin combinations, Osimertinib, and prognostic factors for survival. Without direct data on H002, we cannot conclude its effectiveness compared to other treatments. ^{1 2 3 4 5}

What safety data is available for the treatment H002 for non-small cell lung cancer?

The study titled 'Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer' provides safety data for H002. It involved 58 patients and showed that H2 inhalation could control tumor progression and reduce adverse events associated with chemotherapy, targeted therapy, and immunotherapy. The study was approved by the Ethics Committee of Fuda Cancer Hospital and registered at ClinicalTrials.gov (Identifier: NCT03818347). ^{6 7 8 9 10}

Is the drug H002 a promising treatment for non-small cell lung cancer?

The drug H002 could be promising for non-small cell lung cancer because new treatment combinations, like triplet therapies, have shown potential to improve survival rates beyond current standard treatments. These new approaches are being explored to offer better outcomes for patients. ^{1 11 12 13 14}

Research Team

Louis Zhang

Principal Investigator

RedCloud Bio

Eligibility Criteria

Adults (≥18 years) with advanced non-small cell lung cancer (NSCLC) and specific EGFR mutations who have progressed on certain treatments like osimertinib. They must have measurable disease, a life expectancy of at least 12 weeks, and an ECOG performance status of 0-1. Women able to bear children and men with partners of childbearing potential must commit to effective contraception.

Inclusion Criteria

My cancer progressed despite treatment with a specific lung cancer medication.

You are expected to live for at least 12 more weeks.

My lung cancer has a specific EGFR mutation.

Exclusion Criteria

I have a history of interstitial lung disease.

I have a severe eye condition that hasn't improved to mild or no symptoms.

I have brain metastases, meningeal metastasis, or spinal cord compression that causes symptoms.

Treatment Details

Interventions

• H002

Trial Overview The trial is testing H002, an oral medication for NSCLC patients with active EGFR mutations. It has two phases: Phase I determines the safe dosage while Phase IIa expands the study to more patients at that dose level, assessing safety and preliminary effectiveness against tumors.

Participant Groups

Group I: 80 mg QD, oral Experimental Treatment 1 Intervention

H002 80mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Group II: 40 mg QD, oral Experimental Treatment 1 Intervention

H002 40mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Group III: 350 mg QD, oral Experimental Treatment 1 Intervention

H002 350mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Group IV: 250 mg QD, oral Experimental Treatment 1 Intervention

H002 250mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Group V: 20 mg QD, oral Experimental Treatment 1 Intervention

H002 20mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Group VI: 150 mg QD, oral Experimental Treatment 1 Intervention

H002 150mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Who Is Running the Clinical Trial?

RedCloud Bio

Lead Sponsor

Trials

2

Recruited

150+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

In a study involving 41 patients with advanced non-small-cell lung cancer, a very high-dose, cisplatin-based chemotherapy regimen resulted in a 41% overall objective response rate, with one complete response and 16 partial responses, indicating significant activity against the cancer.

Despite its effectiveness, the regimen was associated with considerable toxicity, including dose-limiting neurologic effects and significant hematologic toxicity, suggesting that while it may offer some benefits, the risks may outweigh the advantages compared to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced non-small cell lung cancer with very high-dose cisplatin combined with etoposide and mitomycin C. Hesketh, PJ., Tansan, S., Caguioa, PB., et al.[2019]

Osimertinib significantly improves progression-free survival (PFS) and overall survival (OS) in patients with advanced nonsmall cell lung cancer (NSCLC) with EGFR mutations, based on a meta-analysis of 6 trials involving various patient subgroups.

Patients with the T790M mutation experienced even greater benefits from Osimertinib, including higher overall response rates and fewer severe adverse events compared to those treated with traditional EGFR-TKIs or chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib or EGFR-TKIs/chemotherapy in patients with EGFR-mutated advanced nonsmall cell lung cancer: A meta-analysis. Huang, L., Huang, H., Zhou, XP., et al.[2022]

In a study of 93 patients with stage II non-small cell lung cancer, factors such as the total number of dissected lymph nodes and the metastasis rate of N1 lymph nodes were found to significantly impact the 5-year survival rate after surgery.

Specifically, having more than 6 dissected lymph nodes and a lower metastasis rate in N1 lymph nodes were associated with better survival outcomes, while a metastasis rate over 50% indicated a poorer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors for surgically managed patients with stage II non-small cell lung cancer. Wang, L., Liu, Y., Xu, S.[2020]

A novel nomogram was developed to predict overall survival in patients with resected N2 non-small cell lung cancer (NSCLC) who underwent neoadjuvant radiotherapy, using data from the SEER database and involving significant variables like age, sex, and treatment type.

The nomogram demonstrated better predictive accuracy and clinical utility compared to the traditional TNM staging system, helping clinicians make more informed treatment decisions for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of a nomogram for predicting overall survival of resected N2 non-small cell lung cancer patients undergoing neoadjuvant radiotherapy. Shi, J., Peng, B., Wang, C., et al.[2023]

In a study of 1280 patients with advanced non-small cell lung cancer (NSCLC), those receiving single-agent therapies (singlets) had a significantly lower overall survival (OS) of 6.3 months compared to patients on combination therapies or other regimens, indicating that more complex treatment strategies may be more effective.

Factors associated with improved OS included being younger than 65 years, female gender, and having a longer interval between first-line and subsequent therapies, while pemetrexed-based therapies and squamous histology were linked to reduced survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying Subsequent Therapies in Patients with Advanced Non-Small Cell Lung Cancer and Factors Associated with Overall Survival. Afanasjeva, J., Hui, RL., Spence, MM., et al.[2018]

In a study involving 58 adult patients with advanced non-small cell lung cancer, hydrogen (H2) inhalation therapy was found to significantly alleviate pulmonary symptoms and reduce adverse events associated with chemotherapy, targeted therapy, and immunotherapy over a 5-month treatment period.

Patients receiving H2 therapy showed improved progression-free survival compared to a control group, indicating that H2 inhalation may be an effective adjunct treatment to enhance the efficacy of standard cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer. Chen, JB., Kong, XF., Mu, F., et al.[2021]

In a phase II study involving 29 patients with advanced non-small-cell lung cancer (NSCLC), the combination of oxaliplatin and docetaxel showed an overall response rate of 37%, indicating its potential efficacy as a treatment option.

The treatment was well tolerated, with no unusual adverse events reported; the most common severe side effects were anemia (14%) and hyperglycemia (10%), suggesting a manageable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oxaliplatin and docetaxel in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC). Raez, LE., Santos, ES., Lopes, G., et al.[2018]

In a phase II study involving 39 patients with inoperable non-small cell lung cancer (NSCLC), the combination of docetaxel and carboplatin showed a promising objective response rate of 35.9%, indicating its efficacy in treating this condition.

The treatment was well tolerated, with major toxicities being leukocytopenia and neutropenia, while severe non-hematological side effects were rare, suggesting a favorable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of combination chemotherapy with docetaxel and carboplatin for patients with advanced or metastatic non-small cell lung cancer. Kasahara, K., Kimura, H., Shibata, K., et al.[2018]

In a study of 16,527 non-small cell lung cancer patients, the most common adverse events linked to pharmacotherapy were hypocalcemia, elevated creatine phosphokinase, and hypertriglyceridemia, highlighting the need for monitoring these conditions during treatment.

The modified Apriori algorithm proved to be more effective than the conventional method in identifying associations between chemotherapy drugs and adverse events, suggesting it could be a valuable tool for improving patient safety in cancer pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovering Associations of Adverse Events with Pharmacotherapy in Patients with Non-Small Cell Lung Cancer Using Modified Apriori Algorithm. Chen, W., Yang, J., Wang, HL., et al.[2022]

In a phase II trial involving 94 patients with early-stage non-small cell lung carcinoma, induction chemotherapy with paclitaxel and carboplatin resulted in a high major objective response rate of 56%, indicating its efficacy as a preoperative treatment.

The treatment was associated with acceptable safety, as 94% of patients underwent surgical exploration and 86% achieved complete resection, with only two postoperative deaths and no unexpected morbidity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction chemotherapy before surgery for early-stage lung cancer: A novel approach. Bimodality Lung Oncology Team. Pisters, KM., Ginsberg, RJ., Giroux, DJ., et al.[2022]

In a study of 53 patients with pN2 non-small cell lung cancer, the three-year and five-year survival rates were found to be 46.8% and 33.4%, indicating a moderate prognosis for this group.

The study revealed that preoperative CT scans had low sensitivity for detecting N factors, with only 45% for squamous cell carcinoma and 24.2% for adenocarcinoma, suggesting that thorough lymph node dissection is more critical than aggressive preoperative staging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical study for improving the survival rate of pN2 lung cancer through our case of 53 patients]. Takahashi, W., Okuwaki, H., Yoshii, S., et al.[2006]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

Cisplatin-based chemotherapy is preferred for treating advanced nonsmall cell lung cancer, with carboplatin as an alternative for patients with contraindications; nonplatinum regimens are also available for those who cannot tolerate platinum-based treatments.

There is no evidence that higher doses of cisplatin improve survival compared to standard doses, and a minimum of four to six cycles of chemotherapy is recommended for patients who respond well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First- and second-line therapy for advanced nonsmall cell lung cancer. Sculier, JP., Moro-Sibilot, D.[2018]

In a study of 240 N2 lung cancer patients, the overall survival rates were 81% at 6 months, but dropped to 23% by 5 years, indicating a significant decline in survival over time.

The type of histology (squamous, adenocarcinoma, adenosquamous) did not significantly affect survival rates, and different treatment combinations (surgery alone or with radiotherapy/chemotherapy) did not show a statistically significant impact on survival, highlighting the importance of radical surgery as a primary treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

["N2" carcinoma of the lung. Therapeutic considerations]. Ugolini, D., Boddi, V., Notaristefano, T., et al.[2006]

References

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

Treatment of advanced non-small cell lung cancer with very high-dose cisplatin combined with etoposide and mitomycin C. [2019]

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

Osimertinib or EGFR-TKIs/chemotherapy in patients with EGFR-mutated advanced nonsmall cell lung cancer: A meta-analysis. [2022]

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

Prognostic factors for surgically managed patients with stage II non-small cell lung cancer. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Development and validation of a nomogram for predicting overall survival of resected N2 non-small cell lung cancer patients undergoing neoadjuvant radiotherapy. [2023]

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

Identifying Subsequent Therapies in Patients with Advanced Non-Small Cell Lung Cancer and Factors Associated with Overall Survival. [2018]

6. Australia pubmed.ncbi.nlm.nih.gov

Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oxaliplatin and docetaxel in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC). [2018]

8. Greece pubmed.ncbi.nlm.nih.gov

A phase II study of combination chemotherapy with docetaxel and carboplatin for patients with advanced or metastatic non-small cell lung cancer. [2018]

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

Discovering Associations of Adverse Events with Pharmacotherapy in Patients with Non-Small Cell Lung Cancer Using Modified Apriori Algorithm. [2022]

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

Induction chemotherapy before surgery for early-stage lung cancer: A novel approach. Bimodality Lung Oncology Team. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

[A clinical study for improving the survival rate of pN2 lung cancer through our case of 53 patients]. [2006]

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

Triplet combination chemotherapy and targeted therapy regimens. [2005]

13. England pubmed.ncbi.nlm.nih.gov

First- and second-line therapy for advanced nonsmall cell lung cancer. [2018]

14. Italy pubmed.ncbi.nlm.nih.gov

["N2" carcinoma of the lung. Therapeutic considerations]. [2006]