TAK-788 for Non-Small Cell Lung Cancer

Not currently recruiting at 94 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medicine called TAK-788, an experimental treatment for individuals with non-small cell lung cancer (NSCLC) or other solid tumors. The trial aims to determine the optimal dose and identify any side effects when combined with chemotherapy. It is open to those with advanced cancer unresponsive to standard treatments, particularly if their tumors have specific genetic changes like EGFR or HER2 mutations. Participants should have a type of cancer that impacts daily life, such as difficulty breathing or persistent coughing, and should not have previously received TAK-788. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new 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.

Is there any evidence suggesting that TAK-788 is likely to be safe for humans?

Research has shown that TAK-788, also known as mobocertinib, can combat tumors and has manageable side effects in patients with advanced non-small cell lung cancer (NSCLC). In studies involving patients with a specific genetic change called EGFR exon 20 insertion mutations, the treatment was generally well-tolerated. Most side effects could be controlled or reduced with treatment.

Participants in these studies often experienced side effects like diarrhea, so this trial includes steps to prevent it. Other side effects were usually not severe, meaning they typically aren't serious enough to stop treatment. Overall, TAK-788 has shown promise in being both effective and safe for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about TAK-788 because it targets specific mutations in non-small cell lung cancer (NSCLC) that are tough to treat with standard therapies. Unlike traditional treatments, which often focus on general chemotherapy or older EGFR inhibitors, TAK-788 is designed to target EGFR exon 20 insertion mutations and HER2 mutations specifically. This precision approach could potentially lead to more effective outcomes for patients whose cancer doesn't respond well to existing treatments, offering hope for those with limited options.

What evidence suggests that TAK-788 could be an effective treatment for non-small cell lung cancer?

Research has shown that TAK-788, also known as mobocertinib, offers promising results for treating non-small cell lung cancer (NSCLC) with specific genetic changes. One study found that 43% of patients with a particular mutation (EGFR exon 20 insertion) experienced significant tumor shrinkage. This trial includes various treatment arms, such as those for participants with EGFR exon 20 activating insertions, HER2 exon 20 activating insertions, and other targets against which TAK-788 is active. However, TAK-788 did not outperform traditional chemotherapy for some patients receiving their first treatment. Common side effects included diarrhea, affecting nearly half of the patients. Despite these side effects, the treatment has proven effective in real-world situations, especially for patients who have tried other treatments without success. ^{3 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

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8295177/

Activity and Safety of Mobocertinib (TAK-788) in Previously ... Among 28 EGFRex20ins patients treated at 160 mg daily, the investigator-assessed confirmed response rate was 43% (12/28; 95% confidence interval (CI): 24–63%) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02716116

NCT02716116 | A Study of TAK-788 in Adults With Non- ... The extension phase will evaluate efficacy of TAK-788 in participants with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04869-X/fulltext

585P Real-world outcomes in patients with non-small cell ... Most patients received mobocertinib as 2nd or 3rd line of therapy (78 [74.3%]); maximum daily dose (N patients (%)): 160mg: 71 (67.6%), 120mg: 16 (15.2%), 80mg: ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39861957/

Patterns of Treatment and Real-World Outcomes ... The most common AE was diarrhea (any grade) (52 patients; 49.5%). Conclusions: These data illustrate the real-world effectiveness of mobocertinib. Keywords: ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01269

First-Line Mobocertinib Versus Platinum-Based ... The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with EGFR ex20ins+ advanced/metastatic NSCLC.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33632775/

Activity and Safety of Mobocertinib (TAK-788) in ... - PubMed Mobocertinib demonstrated antitumor activity with manageable toxicity in patients with advanced EGFRex20ins NSCLC in this study.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02716116

A Study of TAK-788 in Adults With Non-Small Cell Lung ... This phase 1/2 study will evaluate the safety, pharmacokinetics, and anti-tumor activity of oral EGFR/HER2 Inhibitor TAK-788 in participants with NSCLC and anti ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9099

Mobocertinib (TAK-788) in EGFR exon 20 insertion ... Indirect comparison of TAK-788 vs real-world data outcomes in refractory non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04129502

Study Details | NCT04129502 | TAK-788 as First-Line ... 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 ...