TAK-788 vs Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 203 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Millennium Pharmaceuticals, Inc.

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 40 months

354 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare effectiveness of TAK-788 as first-line treatment with that of platinum-based chemotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors has epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Participants will be randomly assigned to one of the two treatment groups- TAK-788 group or Platinum-based chemotherapy group. Participants will receive TAK-788 orally and pemetrexed/cisplatin or pemetrexed/carboplatin via vein until the participants experience worsening disease (PD) as assessed by blinded independent review committee (IRC), intolerable harmful effects or another discontinuation criteria.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain medications like moderate or strong CYP3A inhibitors or inducers within 10 days before starting TAK-788. Also, you should not be on medications known to cause torsades de pointes.

What data supports the effectiveness of the drug TAK-788 for non-small cell lung cancer?

Research shows that drugs like pemetrexed and cisplatin, which are part of the treatment being compared to TAK-788, have been effective in treating non-small cell lung cancer (NSCLC). Pemetrexed combined with cisplatin is a standard treatment for advanced NSCLC, suggesting that TAK-788 is being compared to a well-established and effective regimen. ^{1 2 3 4 5}

What safety data exists for TAK-788 and platinum-based chemotherapy in humans?

Pemetrexed, when combined with cisplatin or carboplatin, has been studied for safety in treating lung cancer and mesothelioma. Common side effects include low blood cell counts, fatigue, nausea, and vomiting. Patients are advised to take vitamins and steroids to reduce severe side effects. ^{2 5 6 7 8}

How is TAK-788 different from other drugs for non-small cell lung cancer?

TAK-788 is a novel drug being compared to traditional platinum-based chemotherapy, which includes drugs like carboplatin and cisplatin, for treating non-small cell lung cancer. Unlike standard treatments, TAK-788 may offer a different mechanism of action, potentially targeting specific mutations in cancer cells, which could make it more effective for certain patients. ^{2 3 4 9 10}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

Adults with advanced non-squamous NSCLC and specific EGFR exon 20 mutations, who haven't had systemic treatment for advanced disease. They should have a life expectancy of at least 3 months, an ECOG performance status of 0-1, adequate organ function, and no other primary malignancies or conditions like spinal cord compression.

Inclusion Criteria

I am fully active or can carry out light work.

I have enough tumor tissue for testing the EGFR exon 20 mutation.

You have at least one visible and measurable abnormality according to specific guidelines.

Exclusion Criteria

I have high blood pressure that is not well-controlled.

I am on medication that could affect my heart rhythm.

I have spinal cord compression or cancer spread to the lining of my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAK-788 or platinum-based chemotherapy until disease progression or intolerable toxicity

Up to 40 months

Multiple visits to the clinic

Follow-up

Participants are monitored for survival, subsequent anticancer therapy, and health status

3 years after the last participant is randomized

Open-label extension (optional)

Participants in the chemotherapy group may cross over to treatment with TAK-788 after disease progression

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Pemetrexed
• TAK-788

Trial Overview The trial is testing the effectiveness of TAK-788 taken orally against platinum-based chemotherapy (pemetrexed with cisplatin or carboplatin) given intravenously in patients with certain genetic mutations in their lung cancer. Participants are randomly assigned to one of these treatments.

Participant Groups

Group I: TAK-788 Group (Arm A) Experimental Treatment 1 Intervention

TAK-788 160 milligram (mg) with or without food, capsules, orally, once daily until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria.

Group II: Platinum-based Chemotherapy Group (Arm B) Active Control 3 Interventions

Pemetrexed 500 milligram per meter square (mg/m\^2) plus cisplatin 75 mg/m\^2, infusion, IV, once on Day 1 of 21-day cycle pemetrexed 500 mg/m\^2 plus carboplatin, infusion, IV, once at a dose calculated to produce area under curve (AUC) of 5 milligram\*minute per milliliter (mg\*min/mL) on Day 1 of 21-day cycle until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria. Pemetrexed/cisplatin or pemetrexed/carboplatin will be repeated every 3 weeks for 4 cycles, followed by maintenance treatment with pemetrexed 500 mg/m\^2, on Day 1 of a 21-day cycle thereafter.

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?

Millennium Pharmaceuticals, Inc.

Lead Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

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]

Pemetrexed is an effective cytotoxic agent approved for first-line treatment of non-small cell lung cancer (NSCLC) in combination with cisplatin, showing promise in phase II and III trials.

The toxicity profile of pemetrexed is comparable to other NSCLC treatments, making it a safe option for patients, and its use in postinduction maintenance therapy is currently being evaluated in a phase III study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer. Ricciardi, S., Tomao, S., de Marinis, F.[2021]

In a study of 148 patients with nonsquamous non-small-cell lung cancer, the progression-free survival (PFS) and response rates were similar for both pemetrexed plus cisplatin (Pem-Cis) and docetaxel plus cisplatin (Doc-Cis) regimens, indicating that both treatments are comparably effective.

However, docetaxel plus cisplatin was associated with a longer median overall survival (13.3 months) compared to pemetrexed plus cisplatin (11.7 months), but this difference was not statistically significant, and the Doc-Cis regimen had a higher incidence of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial. Park, CK., Oh, IJ., Kim, KS., et al.[2018]

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]

In a meta-analysis of 486 patients with advanced non-squamous non-small cell lung cancer, the pemetrexed plus carboplatin regimen at 5 mg/min•mL (PCb5) showed a significantly lower incidence of treatment-emergent adverse events (TEAEs) compared to the 6 mg/min•mL (PCb6) regimen, including less thrombocytopenia, anemia, and fatigue.

Despite the differences in safety profiles, both PCb5 and PCb6 regimens demonstrated similar efficacy outcomes in terms of overall survival and progression-free survival, indicating that PCb5 may be a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. Okamoto, I., Schuette, WH., Stinchcombe, TE., et al.[2018]

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]

In a study of 903 patients with malignant pleural mesothelioma (MPM), pemetrexed combined with cisplatin was found to be generally well tolerated, with a low treatment-associated death rate of 0.8% and an interstitial lung disease (ILD) incidence of 0.9%.

The overall response rate to treatment was 25%, and the six-month survival rate was estimated at 75.9%, indicating that pemetrexed is effective in managing MPM, consistent with previous clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. Kuribayashi, K., Voss, S., Nishiuma, S., et al.[2015]

The combination of gemcitabine and pemetrexed showed promising efficacy in treating non-small cell lung cancer (NSCLC), with a median overall survival of 10.1 months and a 1-year survival rate of 42.6% among 60 patients studied.

This cisplatin-free regimen was well-tolerated, with no treatment-related deaths, although some patients experienced significant toxicities like neutropenia and fatigue, indicating it may be a safer alternative for patients unsuitable for cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed-gemcitabine combination in patients with advanced-stage non-small cell lung cancer. Monnerat, C., Le Chevalier, T., Kelly, K., et al.[2022]

References

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

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). [2020]

2. Greece pubmed.ncbi.nlm.nih.gov

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

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

Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer. [2021]

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

Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. [2018]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Ireland pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. [2015]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Pemetrexed in first-line treatment of non-small cell lung cancer. [2015]

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

Phase II study of pemetrexed-gemcitabine combination in patients with advanced-stage non-small cell lung cancer. [2022]