LP-300 + Chemotherapy for Lung Adenocarcinoma EGFR

(HARMONIC Trial)

Recruiting at 25 trial locations

Overseen By Selin Ergulen

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lantern Pharma Inc.

Must not be taking: CYP2C19, P-gp substrates

Disqualifiers: Small cell, Squamous cell, Cardiac issues, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12-18 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, LP-300, combined with two existing chemotherapy drugs in never smokers with a specific type of lung cancer who did not respond to previous treatments. The goal is to see if this combination improves survival by making the chemotherapy more effective.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but it does mention a 'washout period' for tyrosine kinase inhibitors (TKIs) of at least 5 half-lives or 2 weeks, whichever is shorter. Also, you cannot take medications that are sensitive substrates of CYP2C19 or P-gp transporters.

What data supports the effectiveness of the drug combination LP-300, Carboplatin, and Pemetrexed for lung adenocarcinoma?

Research shows that Pemetrexed, when combined with Carboplatin, has demonstrated antitumor activity and mild toxicity in treating non-small cell lung cancer, which is a type of lung cancer similar to lung adenocarcinoma. ^{1 2 3 4 5}

Is the combination of LP-300 and chemotherapy safe for humans?

Pemetrexed, a drug used in combination with carboplatin for lung cancer, has been shown to have mild side effects when patients take folic acid and vitamin B12 supplements. Common side effects include fatigue, nausea, and vomiting, but these are generally manageable. ^{3 6 7 8 9}

What makes the LP-300 + Chemotherapy drug unique for lung adenocarcinoma?

The LP-300 + Chemotherapy treatment is unique because it combines LP-300, a novel agent, with carboplatin and pemetrexed, which are standard chemotherapy drugs. LP-300 is designed to enhance the effectiveness of chemotherapy by potentially reducing toxicity and improving outcomes, offering a new approach compared to traditional chemotherapy regimens. ^{8 10 11 12 13}

Research Team

Reggie Ewesuedo, MD

Principal Investigator

Lantern Pharma Inc.

Eligibility Criteria

This trial is for never smokers over 18 with advanced lung adenocarcinoma, including those who've had TKI treatment but now show disease progression or can't tolerate TKIs. Participants must have stable CNS metastases, adequate organ function, and no recent serious cardiovascular events. They should not be HIV or hepatitis positive and must agree to use contraception.

Inclusion Criteria

Have you been diagnosed with Stage 3 or Stage 4 non-small cell lung cancer?

Has your disease progressed despite treatment?

Have you ever been a smoker?

Exclusion Criteria

Have you ever been a smoker?

I do not have any active infections, lung issues, uncontrolled high blood pressure, diabetes, seizures, or other serious health problems.

Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

6 patients are enrolled and treated with LP-300 in combination with carboplatin and pemetrexed to assess safety

3 weeks

1 visit (in-person) per cycle

Treatment

Patients are randomized to receive either the investigational arm of LP-300 with carboplatin and pemetrexed or the standard of care arm of carboplatin and pemetrexed. Treatment occurs on Day 1 of a 21-day cycle for 4 to 6 cycles.

12-18 weeks

1 visit (in-person) per cycle

Maintenance

Patients may enter a pemetrexed maintenance phase after the initial treatment cycles

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Carboplatin
• LP-300
• Pemetrexed

Trial Overview The study tests the effectiveness of LP-300 combined with carboplatin and pemetrexed chemotherapy in improving survival without cancer progression compared to just chemotherapy alone. It's an open-label phase II trial involving 90 patients across multiple U.S. centers.

Participant Groups

Group I: LP-300 in Combination with Pemetrexed and Carboplatin Experimental Treatment 3 Interventions

LP-300 (investigational drug) + Pemetrexed and Carboplatin (standard of care chemotherapies) Dosing occurs on Day 1 of a 21-day cycle.

Group II: Pemetrexed and Carboplatin (Standard of Care) Active Control 2 Interventions

Pemetrexed and Carboplatin Only (standard of care chemotherapies) Dosing occurs on Day 1 of a 21-day cycle.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Lantern Pharma Inc.

Lead Sponsor

Trials

4

Recruited

390+

Findings from Research

Pemetrexed is an effective treatment for relapsed or chemotherapy-refractory non-small cell lung cancer (NSCLC), showing similar response and survival rates to taxotere but with less toxicity.

When combined with platinum analogs or other chemotherapy agents like gemcitabine or vinorelbine, pemetrexed produces equivalent responses and overall survival outcomes, suggesting it is a viable option in NSCLC treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of pemetrexed in non-small cell lung cancer. Longo-Sorbello, GS., Chen, B., Budak-Alpdogan, T., et al.[2022]

In a study of 53 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, treatment with pemetrexed plus cisplatin or carboplatin resulted in a median overall survival of 10 months and a median progression-free survival of 6 months.

The treatment was generally well-tolerated, with only a small percentage of patients experiencing severe side effects, such as grade 3 or 4 leukopenia and thrombocytopenia, indicating that pemetrexed combined with platinum-based drugs can be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Zhang, GZ., Jiao, SC., Meng, ZT.[2021]

Pemetrexed, when combined with carboplatin, has shown promising antitumor activity with mild toxicity in phase II clinical trials, but it can lead to serious adverse reactions such as toxic epidermal necrolysis, as seen in a reported case.

Supplementation with folic acid and vitamin B12 is recommended during pemetrexed treatment to help reduce the risk of hematological and gastrointestinal side effects, although severe skin reactions can still occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. Bosch-Barrera, J., Gaztañaga, M., Ceballos, J., et al.[2015]

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]

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, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

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 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]

In a study of 51 patients with malignant pleural mesothelioma, both pemetrexed with carboplatin (AC) and pemetrexed with cisplatin (AP) were found to be effective neoadjuvant chemotherapy regimens, with similar rates of disease control and surgical resection (81% for AC and 79% for AP).

However, the AP regimen was associated with a higher incidence of severe side effects, such as grade 3 anemia and increased fatigue, which could negatively affect patients' overall health and their ability to undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). Pasello, G., Marulli, G., Polo, V., et al.[2015]

The combination of paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

In a study of 21 patients with non-small-cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, the combination of paclitaxel and carboplatin showed no objective responses, indicating minimal effectiveness in this patient population.

Despite the lack of overall response, a few patients (3 out of 5) who had only received single-agent treatment before may have experienced some clinical benefit, suggesting that there could be exceptions in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for previously treated patients with non-small-cell lung cancer. Roa, V., Conner, A., Mitchell, RB.[2019]

In a study of 1135 patients with advanced non-small-cell lung cancer, gemcitabine combined with carboplatin (GC) and gemcitabine with paclitaxel (GP) showed similar overall survival rates to the standard paclitaxel-carboplatin (PC) regimen, with median survival times of 7.9 months for GC, 8.5 months for GP, and 8.7 months for PC.

The GC regimen had a higher incidence of severe hematologic side effects but resulted in lower rates of neurotoxicity and hair loss compared to GP and PC, indicating that while efficacy is similar, the toxicity profiles differ significantly among the treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Treat, JA., Gonin, R., Socinski, MA., et al.[2022]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

References

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

Role of pemetrexed in non-small cell lung cancer. [2022]

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

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. [2015]

4. 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]

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

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

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

FDA drug approval summaries: pemetrexed (Alimta). [2022]

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

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

8. 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]

9. Greece pubmed.ncbi.nlm.nih.gov

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). [2015]

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

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for previously treated patients with non-small-cell lung cancer. [2019]

12. England pubmed.ncbi.nlm.nih.gov

A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. [2022]

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

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]