A Study of TAK-788 in Adults With Non-Small Cell Lung Cancer

  • STATUS
    Recruiting
  • End date
    Mar 13, 2023
  • participants needed
    395
  • sponsor
    Millennium Pharmaceuticals, Inc.
Updated on 31 May 2021
systemic therapy
measurable disease
growth factor
metastasis
pemetrexed
carboplatin
epidermal growth factor receptor
HER2
EGFR
cancer chemotherapy
solid tumour
erbb2
epidermal growth factor
afatinib
stage iv non-small cell lung cancer
lung carcinoma
egfr t790m

Summary

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.

Description

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-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations. The trial will be conducted in three parts: a dose escalation (Part 1), including Part 1A (dose escalation combination component of TAK-788 in combination with Pemetrexed/Carboplatin) and Part 1B (TAK-788 monotherapy and TAK-788 in combination with pemetrexed/carboplatin with primary antidiarrhea prevention with loperamide.) and expansion phase (Part 2), followed by an extension phase (Part 3).

The objectives of the dose escalation phase (Part 1),dose escalation combination phase (Part 1A, only for selected sites in the United States) and Antidiarrhea Prophylaxis Cohorts ( part 1B, only for selected sites in the United States) are to determine the safety profile of orally administered TAK-788 and TAK-788 in combination with Pemetrexed/Carboplatin, including the MTD, DLTs, RP2D,pharmacokinetic profile and with loperamide as primary antidiarrhea prevention incidence and severity of TAK-788-associated diarrhea and anti-tumor activity of TAK-788 (Part 1B) . The primary goal of the expansion component of the trial is to evaluate the anti-tumor activity of TAK-788 in seven histologically and molecularly defined cohorts at the RP2D (determined based on dose escalation phase of the trial).

The seven expansion cohorts will be:

  1. NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR TKI, and who have no active, measurable CNS metastases;
  2. NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases;
  3. NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases;
  4. 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;
  5. 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;
  6. 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; and
  7. Participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active, without active CNS metastases.

The extension phase will evaluate efficacy of TAK-788 in participants with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and who have been previously treated. The study will enroll approximately 395 participants.

Details
Condition Non-Small Cell Lung Cancer
Treatment carboplatin, Pemetrexed, AP32788, TAK-788
Clinical Study IdentifierNCT02716116
SponsorMillennium Pharmaceuticals, Inc.
Last Modified on31 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

dose escalation, antidiarrhea
prophylaxis, dose escalation combination, expansion, and extension
Have histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC disease (Stage IIIB or IV) or other solid tumors. For all cohorts except Expansion Cohort 7, the locally advanced or metastatic disease is NSCLC. For Expansion Cohort 7, the locally advanced or metastatic disease is any solid tumor other than NSCLC
Must have sufficient tumor tissue available for analysis
Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1
Male or female adult participants (aged 18 years or older, or as defined per local regulations)
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Minimum life expectancy of 3 months or more
Adequate organ function at baseline
Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected (Fridericia) (QTcF) of less than or equal to (<=) 450 millisecond (ms) in males or <=470 ms in females
Willingness and ability to comply with scheduled visits and study procedures
Part 1: Dose Escalation Cohort Specific Inclusion Criteria
Refractory to standard available therapies
Part 1A: Combination dose escalation cohorts
Participants who have a documented EGFR activating mutation by a local test
Participants with an
Participants with an o EGFR exon 20 insertion, with or without prior anticancer treatments
EGFR exon 20 insertion, with or without prior anticancer treatments
EGFR mutation other than exon 20 insertions, failed or not tolerated prior anticancer therapies
Prior EGFR TKIs are allowed for all participants
Part 1B Cohort 1: Antidiarrhea prophylaxis, monotherapy
Part 2: Expansion Cohort 1 Specific Inclusion Criteria
Have a documented EGFR in-frame exon 20 insertion by a local test,including A763_Y764insFQEA, V769_D770insASV, D770_N771insNPG, D770_N771insSVD, H773_V774insNPH, or any other in-frame exon 20 insertion mutation. The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease
Prior treatment with an EGFR TKI is allowed for all participants. Part 1B Cohort 2: Antidiarrhea prophylaxis, combination dose with chemotherapy
Prior treatment with an EGFR TKI is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician
Have a documented EGFR activating mutation by a local test,including exon 20 insertions, exon 19 deletions or exon 21 L858R substitution (with or without T790M), or an uncommon activating mutation including G719X (where X is any other amino acid), S768I, L861Q, or L861R, more specifically
Expansion Cohort 2 Specific Inclusion Criteria
Have one of the following documented by a local test
A HER2 exon 20 insertion
EGFR mutation other than exon 20 insertions, failed or not tolerated prior anticancer therapies
Prior EGFR TKIs are allowed for all participants
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease
Have a documented EGFR in-frame exon 20 insertion by a local test
Part 2: Expansion Cohort 3 Specific Inclusion Criteria
Have one of the following documented by a local test
An EGFR exon 20 insertion
A HER2 exon 20 insertion
An activating point mutation in HER2
For participants with an EGFR exon 20 insertion: prior treatment with an EGFR TKI is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician
For participants with a HER2 exon 20 insertion or HER2 activating point mutation: prior treatment with a pan-HER TKI (example, afatinib, neratinib, or dacomitinib) is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI
With an EGFR exon 20 insertion: Prior treatment with a pan-HER TKI (example, afatinib, neratinib, or dacomitinib) is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician
Have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions
Have at least one target (that is, measurable) intracranial CNS lesion (greater than or equal to [>=]10 millimeter [mm] in longest diameter by contrast enhanced magnetic resonance imaging [MRI])
Part 2: Expansion Cohort 4 Specific Inclusion Criteria
Have one of the following documented by a local test: an activating mutation in EGFR including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or an uncommon activating mutation other than exon 20 insertion including, but not limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R
Treatment naive for locally advanced or metastatic disease or previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease
An activating point mutation in HER2. 2. Previously treated with one or more regimen of systemic therapy for locally advanced or metastatic disease
Part 2: Expansion Cohort 5 Specific Inclusion Criteria
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
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease
Previously showed an objective response to an EGFR TKI, and subsequently progressed as assessed by the investigator or treating physician
Part 2: Expansion Cohort 6 Specific Inclusion Criteria
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
Have a documented EGFR in-frame exon 20 insertion by a local test. 2. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease
No prior systemic treatment for locally advanced or metastatic disease
Part 2: Expansion Cohort 7 Specific Inclusion Criteria
Participants with solid tumors other than NSCLC with EGFR/HER2 mutations
against which TAK-788 is active, without active CNS metastases
Have a solid tumor that is not NSCLC, including, but not limited to, bladder/urinary tract cancer, breast cancer, gastric/esophageal cancer, biliary tract cancer, and head and neck cancer
Have a documented EGFR in-frame exon 20 insertion by a local test
Part 3: Extension Cohort Specific Inclusion Criteria
Have a documented EGFR in-frame exon 20 insertion by a local test and sufficient tumor tissue available for central analysis
Must have received at least 1 prior line of therapy for locally advanced or metastatic disease and no more than 2 regimens of systemic anticancer chemotherapies for locally advanced or metastatic disease
Prior treatment with an EGFR TKI is allowed unless the participant had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI
Is refractory to standard therapy. 3. Have EGFR or HER2 mutations, documented by a local test

Exclusion Criteria

Previously received TAK-788
Received small-molecule anticancer therapy (including cytotoxic chemotherapy, and investigational agents, <=14 days prior to first dose of TAK-788 (except for reversible EGFR TKIs [that is, erlotinib or gefitinib], which are allowed in the dose escalation and expansion cohorts up to 7 days prior to the first dose of TAK-788)
Received antineoplastic monoclonal antibodies including immunotherapy within 28 days of the first dose of TAK-788
Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy
administered outside the chest and brain, stereotactic radiosurgery (SRS), and
stereotactic body radiotherapy are allowed up to 7 days prior to the first
Note: This exclusion criteria does not apply to Expansion Cohort 7. 5
Received radiotherapy <=14 days prior to the first dose of TAK-788 or has not
CYP3A inducer within 10 days prior to first dose of TAK-788
recovered from radiotherapy-related toxicities. Palliative radiation
\. Have undergone major surgery within 28 days prior to first dose of
TAK-788. Minor surgical procedures, such as catheter placement or minimally
invasive biopsy, are allowed
dose 6. Received a moderate or strong CYP4503A inhibitor or moderate or strong
\. Part 1 (dose escalation), Part 1A (dose escalation combination), Part 1B
Part 3 (extension cohort) and Expansion Cohorts 4 to 7 of Part 2 (expansion
(antidiarrheal prophylaxis) and Expansion Cohorts 1 to 3 of Part 2 (expansion
phase)
phase) only: Have symptomatic CNS metastases at screening or asymptomatic
only
disease requiring corticosteroids to control symptoms within 7 days prior to
Have known active brain metastases (have either previously untreated
the first dose of TAK-788
intracranial CNS metastases or previously treated intracranial CNS metastases
with radiologically documented new or progressing CNS lesions). Brain
metastases are allowed if they have been treated with surgery and/or radiation
and have been stable without requiring corticosteroids to control symptoms
within 7 days before the first dose of TAK-788, and have no evidence of new or
enlarging brain metastases
\. Have current spinal cord compression (symptomatic or asymptomatic and
detected by radiographic imaging) or leptomeningeal disease (symptomatic or
asymptomatic)
hypertension should be under treatment on study entry to control blood
pressure
\. Have prolonged QTcF interval, or being treated with medications known to
\. Have significant, uncontrolled, or active cardiovascular disease. 11
be associated with the development of Torsades de Pointes
Have a known history of uncontrolled hypertension. Participants with
\. Have an ongoing or active infection, including but not limited to, the
requirement for intravenous (IV) antibiotics, or a known history of human
immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus
(HCV). Testing is not required in the absence of history
\. Currently have or have a history of interstitial lung disease, radiation
pneumonitis that required steroid treatment, or drug-related pneumonitis
\. Female participants who are lactating and breastfeeding or have a
positive urine or serum pregnancy test during the screening period
Note: Female participants who are lactating will be eligible if they
\. Have any condition or illness that, in the opinion of the investigator
might compromise participant safety or interfere with the evaluation of the
discontinue breastfeeding. 16. Have gastrointestinal illness or disorder that
safety of the drug
could affect oral absorption of TAK-788
Have a history of or suspected severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs
Part 1A: Combination dose escalation cohorts
Received a live vaccine within 4 weeks before randomization (per USPIs for pemetrexed and carboplatin)
Grade >2 peripheral neuropathy National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0)
Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with evaluation of the study drug; this should include known contraindications mentioned in the United States prescribing information (USPIs) for pemetrexed, and carboplatin
Part 1B Cohort 1: Antidiarrhea prophylaxis, monotherapy 1. In addition to the
uncontrolled, or active cardiovascular disease, restrictions above; cardiac
ejection fraction less than (<) 50% by echocardiogram or MUGA scan
Part 1B Cohort 2: Antidiarrhea prophylaxis, combination dose with chemotherapy
Grade >2 peripheral neuropathy
Received a live vaccine within 4 weeks before randomization (per USPIs for pemetrexed and carboplatin)
In addition to the uncontrolled, or active cardiovascular disease, restrictions above; cardiac ejection fraction less than (<) 50% by echocardiogram or MUGA scan
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