TAK-788 for Non-Small Cell Lung Cancer

Recruiting at 84 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Millennium Pharmaceuticals, Inc.

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Other malignancy, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

334 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study is about a medicine called TAK-788, also known as mobocertinib, given to adults with non-small cell lung cancer. The main aims of this study are to check if there are any side effects from TAK-788, to learn how TAK-788 is processed by the body, and to determine the best dose of TAK-788 to treat this condition. Participants will take TAK-788 capsules with chemotherapy. Participants will continue to take TAK-788 unless they or their doctor decide they should stop this treatment. Participants will take TAK-788 capsules with or without chemotherapy under antidiarrhea prevention to determine the safety of TAK-788 treatment. Non-Asian, non-White participants will take TAK-788 to determine the safety and tolerability of TAK-788 treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot have taken certain cancer treatments or medications affecting liver enzymes shortly before starting the trial. It's best to discuss your current medications with the trial team.

How is the drug TAK-788 unique for treating non-small cell lung cancer?

TAK-788 is unique because it targets specific genetic mutations in non-small cell lung cancer, offering a precision medicine approach that may be more effective for patients with these mutations compared to standard treatments. ^{1 2 3 4 5}

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

Research shows that lung cancer cells with a specific genetic deficiency (loss of function of the Clusterin gene) are highly sensitive to TAK1 inhibitors, which are similar to TAK-788. This suggests that TAK-788 might be effective in treating certain types of lung cancer with similar genetic profiles. ^{1 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer (NSCLC) who have specific genetic mutations in their tumors and haven't responded to standard treatments can join. They must have a normal heart rhythm, adequate organ function, and at least a 3-month life expectancy. Those with certain other cancers or active brain metastases cannot participate.

Inclusion Criteria

I am willing and able to follow the study's schedule and procedures.

My condition hasn't improved with standard treatments.

Your heart's electrical activity is normal on the screening test.

Exclusion Criteria

I have no other cancers except for certain skin, cervical, or treated prostate cancers.

I haven't taken strong or moderate CYP3A affecting drugs in the last 10 days.

I have previously been treated with TAK-788.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the safety profile of TAK-788, including MTD, DLTs, RP2D, and pharmacokinetic profile

8-12 weeks

Expansion

Evaluate the anti-tumor activity of TAK-788 in seven histologically and molecularly defined cohorts

16-24 weeks

Extension

Evaluate efficacy of TAK-788 in participants with previously treated locally advanced or metastatic NSCLC

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAK-788

Trial Overview The trial is testing TAK-788 (mobocertinib), which participants will take as capsules possibly combined with chemotherapy. The study aims to find the best dose by assessing side effects, how the body processes it, and its safety across different patient groups.

How Is the Trial Designed?

Group I: Part 3: Extension Cohort Experimental Treatment 1 Intervention

TAK-788 treatment for participants with previously treated locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations.

Group II: Part 2: Expansion Cohort 7 Experimental Treatment 1 Intervention

TAK-788 treatment for participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active without active CNS metastases.

Group III: Part 2: Expansion Cohort 6 Experimental Treatment 1 Intervention

TAK-788 treatment NSCLC participants with EGFR exon 20 activating insertions, who have not received prior systemic anticancer treatment for locally advanced or metastatic disease without active CNS metastases

Group IV: Part 2: Expansion Cohort 5 Experimental Treatment 1 Intervention

TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have previously shown an objective response to an EGFR TKI and subsequently progressed without active CNS metastases.

Group V: Part 2: Expansion Cohort 4 Experimental Treatment 1 Intervention

TAK-788 treatment for NSCLC participants with other targets against which TAK-788 is active (examples include EGFR exon 19 deletions or exon 21 substitutions \[with or without T790M mutations\] and other uncommon EGFR activating mutations), without active CNS metastases.

Group VI: Part 2: Expansion Cohort 3 Experimental Treatment 1 Intervention

TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases.

Group VII: Part 2: Expansion Cohort 2 Experimental Treatment 1 Intervention

TAK-788 treatment for NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases.

Group VIII: Part 2: Expansion Cohort 1 Experimental Treatment 1 Intervention

TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR tyrosine kinase inhibitors (TKI), and who have no active, measurable central nervous system (CNS) metastases.

Group IX: Part 1: Dose Escalation Component Experimental Treatment 1 Intervention

TAK-788 treatment for participants with advanced NSCLC.

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

Published Research Related to This Trial

In a phase II study involving 20 patients with locally advanced non-small cell lung cancer, the combination of weekly paclitaxel and cisplatin with thoracic radiotherapy showed a 43.8% objective response rate, indicating some efficacy in treating this aggressive cancer.

However, the treatment was associated with a high incidence of severe toxicities (75% of patients experienced grade 3/4 side effects), leading to early discontinuation of treatment for some patients and ultimately prompting the study's closure due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of weekly paclitaxel, cisplatin and concurrent radiation therapy for locally-advanced unresectable non-small cell lung cancer: early closure due to lack of efficacy. Park, SH., Kim, MK., Kyung, SY., et al.[2021]

In a study of 231 patients with advanced non-squamous non-small-cell lung cancer (NSCLC), TTF1 expression and PD-L1 status were identified as important biomarkers that can help predict patient outcomes, specifically progression-free survival (PFS) and overall survival (OS) when treated with immune checkpoint inhibitors (ICIs).

The research found that patients lacking TTF1 expression, having a Lung Immune Prognostic Index (LIPI) score greater than 0, receiving treatment beyond the first line, and those with liver metastases had poorer PFS, highlighting the potential of these biomarkers to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of Thyroid Transcription Factor-1 expression in lung adenocarcinoma in patients treated with anti PD-1/PD-L1. Galland, L., Le Page, AL., Lecuelle, J., et al.[2022]

Researchers discovered new gene fusions involving the NTRK1 gene in 3.3% of lung cancer patients, which lead to the activation of the TRKA protein, promoting cancer growth.

Inhibiting TRKA kinase activity in cells with these NTRK1 fusions effectively reduced cell growth and autophosphorylation, suggesting a potential therapeutic target for treating this subset of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Vaishnavi, A., Capelletti, M., Le, AT., et al.[2022]

The selective pan-NTRK inhibitor AZD7451 significantly inhibited the growth of colorectal cancer cells with an NTRK1 fusion (KM12) at a low concentration of 2 nM, demonstrating its potential as an effective treatment for tumors with NTRK fusions.

In contrast, AZD7451 had no inhibitory effect on the H810 cell line, which expressed low levels of NTRK1-3, suggesting that the efficacy of NTRK inhibitors may depend on the presence of specific NTRK fusions or expressions in lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of neurotrophic tyrosine kinase receptor 1 fusions and neurotrophic tyrosine kinase receptor family expression in non-small-cell lung cancer and sensitivity to AZD7451 in vitro. Tatematsu, T., Sasaki, H., Shimizu, S., et al.[2021]

Neurotrophic tyrosine kinase (NTRK) gene fusions, although found in less than 5% of lung tumors, are significant oncogenic drivers associated with poor survival, highlighting their potential as therapeutic targets in lung cancer.

Clinical trials of NTRK inhibitors like entrectinib and LOXO-101 have shown promising responses in lung cancer patients with an acceptable safety profile, suggesting these treatments could be effective options for targeting specific lung cancer subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New targets bring hope in squamous cell lung cancer: neurotrophic tyrosine kinase gene fusions. Rolfo, C., Raez, L.[2023]

Citations

1. Australia pubmed.ncbi.nlm.nih.gov

Inactivation of tumor suppressor gene Clusterin leads to hyperactivation of TAK1-NF-κB signaling axis in lung cancer cells and denotes a therapeutic opportunity. [2021]

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

A phase II study of weekly paclitaxel, cisplatin and concurrent radiation therapy for locally-advanced unresectable non-small cell lung cancer: early closure due to lack of efficacy. [2021]

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

Prognostic value of Thyroid Transcription Factor-1 expression in lung adenocarcinoma in patients treated with anti PD-1/PD-L1. [2022]

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

A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments. [2022]

5. China pubmed.ncbi.nlm.nih.gov

A single-arm, prospective study of apatinib mesylate plus pemetrexed in patients of advanced non-squamous non-small cell lung cancer after failure of previous chemotherapy. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Palliative Hypofractionated Radiotherapy For Non-small-cell Lung Cancer (NSCLC) Patients Previously Treated By Induction Chemotherapy. [2021]

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

Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. [2022]

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

Investigation of neurotrophic tyrosine kinase receptor 1 fusions and neurotrophic tyrosine kinase receptor family expression in non-small-cell lung cancer and sensitivity to AZD7451 in vitro. [2021]

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

New targets bring hope in squamous cell lung cancer: neurotrophic tyrosine kinase gene fusions. [2023]