Trial Search Results

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

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Millennium Pharmaceuticals, Inc.

Collaborator: Takeda

Intervention(s):

  • Drug: TAK-788
  • Drug: Pemetrexed
  • Drug: Carboplatin

Phase:

Phase 1/Phase 2

Eligibility


General Inclusion Criteria all cohorts: dose escalation, antidiarrhea prophylaxis, dose
escalation combination, expansion, and extension:

   1. 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.

   2. Must have sufficient tumor tissue available for analysis.

   3. Must have measurable disease by response evaluation criteria in solid tumors (RECIST)
   v1.1.

   4. Male or female adult participants (aged 18 years or older, or as defined per local
   regulations).

   5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

   6. Minimum life expectancy of 3 months or more.

   7. Adequate organ function at baseline.

   8. 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.

   9. Willingness and ability to comply with scheduled visits and study procedures.

Part 1: Dose Escalation Cohort Specific Inclusion Criteria:

1. Refractory to standard available therapies.

Part 1A: Combination dose escalation cohorts

   1. Participants who have a documented EGFR activating mutation by a local test.

   2. Participants with an o EGFR exon 20 insertion, with or without prior anticancer
   treatments.

   o EGFR mutation other than exon 20 insertions, failed or not tolerated prior
   anticancer therapies.

   3. Prior EGFR TKIs are allowed for all participants.

Part 1B Cohort 1: Antidiarrhea prophylaxis, monotherapy

   1. 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.

   2. Previously treated with one or more regimens of systemic therapy for locally advanced
   or metastatic disease.

   3. Prior treatment with an EGFR TKI is allowed for all participants. Part 1B Cohort 2:
   Antidiarrhea prophylaxis, combination dose with chemotherapy

   1. 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.

   2. Participants with an

   o EGFR exon 20 insertion, with or without prior anticancer treatments.

   o EGFR mutation other than exon 20 insertions, failed or not tolerated prior
   anticancer therapies.

   3. Prior EGFR TKIs are allowed for all participants.

Part 2: Expansion Cohort 1 Specific Inclusion Criteria:

   1. 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.

   3. 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.

Expansion Cohort 2 Specific Inclusion Criteria:

   1. Have one of the following documented by a local test:

      1. A HER2 exon 20 insertion;

      2. An activating point mutation in HER2.

   2. Previously treated with one or more regimens of systemic therapy for locally advanced
   or metastatic disease.

   3. 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.

Part 2: Expansion Cohort 3 Specific Inclusion Criteria:

1. Have one of the following documented by a local test:

   1. An EGFR exon 20 insertion;

   2. A HER2 exon 20 insertion;

   3. An activating point mutation in HER2. 2. Previously treated with one or more regimen
   of systemic therapy for locally advanced or metastatic disease.

   3. 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.

   4. 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.

   5. Have either previously untreated intracranial CNS metastases or previously treated
   intracranial CNS metastases with radiologically documented new or progressing CNS
   lesions.

   6. 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:

      1. 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.

      2. 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.

   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.

   1. 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.

   3. 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.

      1. Have a documented EGFR in-frame exon 20 insertion by a local test.

      2. 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.

   1. 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.

   2. Is refractory to standard therapy. 3. Have EGFR or HER2 mutations, documented by a
   local test.

   Part 3: Extension Cohort Specific Inclusion Criteria:

   1. Have a documented EGFR in-frame exon 20 insertion by a local test and sufficient
   tumor tissue available for central analysis.

   2. 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.

   o 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.

   Exclusion Criteria:

      1. Previously received TAK-788.

      2. 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).

      3. Received antineoplastic monoclonal antibodies including immunotherapy within 28
      days of the first dose of TAK-788.

      4. 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.

   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 recovered from
   radiotherapy-related toxicities. Palliative radiation administered outside the chest
   and brain, stereotactic radiosurgery (SRS), and stereotactic body radiotherapy are
   allowed up to 7 days prior to the first dose 6. Received a moderate or strong CYP4503A
   inhibitor or moderate or strong CYP3A inducer within 10 days prior to first dose of
   TAK-788.

   7. 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.

   8. Part 1 (dose escalation), Part 1A (dose escalation combination), Part 1B
   (antidiarrheal prophylaxis) and Expansion Cohorts 1 to 3 of Part 2 (expansion phase)
   only: Have symptomatic CNS metastases at screening or asymptomatic disease requiring
   corticosteroids to control symptoms within 7 days prior to the first dose of TAK-788.

   Part 3 (extension cohort) and Expansion Cohorts 4 to 7 of Part 2 (expansion phase)
   only:

   Have known active brain metastases (have either previously untreated 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.

   9. Have current spinal cord compression (symptomatic or asymptomatic and detected by
   radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).

   10. Have significant, uncontrolled, or active cardiovascular disease. 11. Have a known
   history of uncontrolled hypertension. Participants with hypertension should be under
   treatment on study entry to control blood pressure.

   12. Have prolonged QTcF interval, or being treated with medications known to be
   associated with the development of Torsades de Pointes.

   13. 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.

   14. Currently have or have a history of interstitial lung disease, radiation
   pneumonitis that required steroid treatment, or drug-related pneumonitis.

   15. 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 discontinue
   breastfeeding. 16. Have gastrointestinal illness or disorder that could affect oral
   absorption of TAK-788.

   17. Have any condition or illness that, in the opinion of the investigator, might
   compromise participant safety or interfere with the evaluation of the safety of the
   drug.

   Part 1A: Combination dose escalation cohorts

      1. Have a history of or suspected severe hypersensitivity reaction to
      platinum-containing drugs, pemetrexed, or any known excipients of these drugs.

      2. Grade >2 peripheral neuropathy National Cancer Institute Common Terminology
      Criteria for Adverse Events (NCI CTCAE version 5.0).

      3. 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.

      4. Received a live vaccine within 4 weeks before randomization (per 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

      1. Grade >2 peripheral neuropathy

      2. Received a live vaccine within 4 weeks before randomization (per USPIs for
      pemetrexed and carboplatin).

      3. In addition to the uncontrolled, or active cardiovascular disease, restrictions
      above; cardiac ejection fraction less than (<) 50% by echocardiogram or MUGA
      scan.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Grace Hwang
650-723-0437
Recruiting