Breast Cancer Clinical Trial

A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors

Summary

This study is about TAK-500, given either alone or with pembrolizumab, in adults with select locally advanced or metastatic solid tumors.

The aims of the study are:

to assess the safety profile of TAK-500 when given alone and when given with pembrolizumab.
to assess the effects of TAK-500, when given alone and when given with pembrolizumab, on adults with locally advanced or metastatic solid tumors.

Participants may receive TAK-500 for up to 1 year. Participants may continue with their treatment if they have continuing benefit and if this is approved by their study doctor. Participants who are receiving TAK-500 either alone or with pembrolizumab will continue with their treatment until their disease progresses or until they or their study doctor decide they should stop this treatment.

View Full Description

Full Description

The drug being tested in this study is called TAK-500. The study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of TAK-500 when used as a single agent (SA) and in combination with pembrolizumab in participants with locally advanced or metastatic solid tumors.

The study will be conducted in 2 phases: Dose Escalation and Dose Expansion Phase. The study will enroll approximately 313 participants (approximately 82 in the Dose Escalation Phase and approximately 231 in Dose Expansion Phase). The dose escalation phase will determine the recommended dose of TAK-500 along with the combination agents for the dose expansion phase. All the participants will be assigned to one of the 9 arms:

Dose Escalation: TAK-500 Single Agent (SA)
Dose Escalation: TAK-500 + Pembrolizumab
Dose Expansion: 2L NSCLC: TAK-500 recommended dose 1 for expansion (RDE 1) + Pembrolizumab
Dose Expansion: 2L NSCLC: TAK-500 recommended dose 2 for expansion (RDE 2) + Pembrolizumab
Dose Expansion: 3L NSCLC: TAK-500 (RDE 1) SA
Dose Expansion: 3L NSCLC: TAK-500 (RDE 2) SA
Dose Expansion: 2L Pancreatic Adenocarcinoma: TAK-500 (RDE 1) + Pembrolizumab
Dose Expansion: 2L Pancreatic Adeno: TAK-500 (RDE 1) SA
Dose Expansion: 3L RCC: TAK-500 (RDE 1) + Pembrolizumab

This multi-center trial will be conducted globally. Participants with demonstrated clinical benefit may continue treatment beyond 1 year if approved by the sponsor.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. 2. Individuals with the following pathologically confirmed (cytological diagnosis is adequate) select locally advanced or metastatic solid tumors, whose disease has progressed on or are intolerant to standard therapy:

Gastroesophageal (esophageal, gastroesophageal junction, and gastric) adenocarcinoma, pancreatic adenocarcinoma, hepatocellular carcinoma (HCC), nonsquamous non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), mesothelioma, triple-negative breast cancer (TNBC), renal clear cell carcinoma (RCC) and nasopharyngeal carcinoma (NPC). Participants who are intolerant to all standard therapies are those who have developed clinical or laboratory abnormalities that prevent continued drug administration as evaluated by the principal investigator at the time of screening.

For dose expansion in 2L nonsquamous NSCLC (TAK-500 plus pembrolizumab):

Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic nonsquamous NSCLC.
Participants may not have a known targetable driver mutation, rearrangement or amplification (eg, EGFR, ALK, MET, ROS1, BRAF, KRASG12C, etc.).

Must have had disease progression while on or following 1 prior line of therapy:

1. Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting.

OR Disease progression/recurrence within 6 months of the completion of anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting.

Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or chemotherapy (eg, carboplatin and pemetrexed).

• Participants are eligible regardless of PD-L1 status.

For dose expansion in 3L nonsquamous NSCLC (TAK-500 SA):

Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic nonsquamous NSCLC.
Participants may not have a known targetable driver mutation, rearrangement or amplification (eg, EGFR, ALK, MET, ROS1, BRAF, KRASG12C, etc.).

Must have had disease progression while on or following 2 prior lines of therapy:

Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting OR Disease progression/recurrence within 6 months of the completion of 1 prior anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting.

Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or chemotherapy (eg, carboplatin and pemetrexed).

Participants must have had disease progression while on or after 1 or 2 lines of chemotherapy in the recurrent locally advanced or metastatic setting. If the anti-PD-(L)1 therapy is given in combination with chemotherapy, participant must have progressed on an additional line of chemotherapy.
Participants are eligible regardless of PD-L1 status.

For dose expansion in 2L pancreatic adenocarcinoma (TAK-500 SA and TAK-500 plus pembrolizumab):

• Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic pancreatic adenocarcinoma.

• Must have had disease progression while on or following 1 prior line of therapy:

1. One prior line of fluorouracil- or gemcitabine-based chemotherapy (eg, FOLFIRINOX, FOLFOX, FOLFIRI, gemcitabine/nab-paclitaxel) in the metastatic/recurrent locally advanced setting.

Prior chemotherapy in the neoadjuvant/adjuvant setting does not qualify unless the participant had progression of disease within 6 months of completion of neoadjuvant/adjuvant chemotherapy.

• Must not have had prior exposure to anti-PD-(L)1 therapy.

• Participants with MSI-H/dMMR disease are not eligible.

• Participants are eligible regardless of PD-L1 status.

For dose expansion in 3L RCC (TAK-500 plus pembrolizumab):

Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic RCC.

Must have had disease progression while on or following 2 prior lines of therapy:

Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting.

OR Disease progression/recurrence within 6 months of the completion of anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting.

Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or an anti-VEGFR TKI.

Participants must have had prior therapy with 1 or 2 lines of VEGFR TKIs in the metastatic/recurrent locally advanced setting. If anti-PD-(L)1 therapy was given in combination with a VEGFR TKI, the participant must have had progressive disease on an additional line of therapy (eg, VEGFR TKI or VEGFR TKI-containing combination).

Participants are eligible regardless of PD-L1 status. 3. Must have at least 1 RECIST version 1.1 measurable lesion. Lesions in previously irradiated areas (or other local therapy) should not be selected as measurable/target lesions unless there has been demonstrated radiographic progression in that lesion. RECIST v1.1 target lesions must include at least 1 lesion that was not previously irradiated.

4. Adequate bone marrow, renal, and hepatic functions, as determined by the following laboratory parameters:

Absolute neutrophil count (ANC) greater than or equal to (>=) 1000/microliter (mcL), platelet count >=75,000/mcL, and hemoglobin >= 8.0 grams per deciliter (g/dL) without growth factor support for ANC or transfusion support for platelets within 14 days before the first study treatment dose.
Total bilirubin <=1.5 times the institutional upper limit of normal (ULN). For participants with Gilbert's disease or HCC, <=3 milligrams per deciliter (mg/dL).
Serum alanine aminotransferase and aspartate aminotransferase <=3.0*ULN or <=5.0*ULN with liver metastases or HCC.
Albumin >=3.0 g/dL.

Calculated creatinine clearance using the Cockcroft-Gault formula >=30 mL/minute.

5 . Left ventricular ejection fraction (LVEF) >50%, as measured by echocardiogram or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.

6. For participants with HCC only: Child-Pugh score less than or equal to 7 (Child-Pugh A or B7).

7. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy.

8. Participants previously treated with fully human/humanized antineoplastic monoclonal antibodies must not have received treatment with such antibodies for at least 4 weeks or the time period equal to the dosing interval, whichever is shorter. No washout period is required for prior treatment with pembrolizumab or other anti-programmed cell death protein 1 (PD-1) antibodies, although the first study dose of these drugs must not occur at an interval less than standard of care (that is, 3 weeks for 200 mg of IV pembrolizumab).

Exclusion Criteria:

History of any of the following <=6 months before first dose of study drug(s): congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, persistent hypertension >=160/100 millimeters of mercury (mmHg) despite optimal medical therapy, ongoing cardiac arrhythmias of Grade >2 (including atrial flutter/fibrillation or intermittent ventricular tachycardia), other ongoing serious cardiac conditions (example, Grade 3 pericardial effusion or Grade 3 restrictive cardiomyopathy), or symptomatic cerebrovascular events. Chronic, stable atrial fibrillation on stable anticoagulation therapy, including low molecular-weight heparin, is allowed.
QT interval with Fridericia correction method >450 milliseconds (men) or >475 milliseconds (women) on a 12- lead ECG during the screening period.
Grade >=2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 predose assessment.
Oxygen saturation <92% on room air at screening or during C1D1 predose assessment.
Treatment with other STING agonists/antagonists, Toll-like receptor agonists or CCR2 agonist/antagonist within the past 6 months.
Active diagnosis of pneumonitis, interstitial lung disease, severe chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lung diseases, acute pulmonary embolism, or Grade >=2 pleural effusion not controlled by tap or requiring indwelling catheters.
Grade >=2 fever of malignant origin.
Chronic, active hepatitis (example, participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV] RNA).
History of hepatic encephalopathy.
Prior or current clinically significant ascites, as measured by physical examination, that requires active paracentesis for control.
Treatment with any investigational products or other anticancer therapy (including chemotherapy, targeted agents, and immunotherapy), within 14 days or 5 half-lives, whichever is shorter, before C1D1 of study drug(s).
Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic treatment with radionuclides within 42 days before C1D1 of study drug(s). Participants with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible.

Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 14 days of C1D1 of study drug(s), with the following exceptions:

Topical, intranasal, inhaled, ocular, intra-articular, and/or other nonsystemic corticosteroids.
Physiological doses of replacement steroid therapy (example, for adrenal insufficiency), not to exceed the equivalent of 10 mg prednisone daily.
Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.

Additional criteria specific for participants in TAK-500 and pembrolizumab combination arm only:

Contraindication to the administration of a pembrolizumab or prior intolerance to pembrolizumab or other anti-PD-1 or anti-programmed cell death protein ligand 1 antibody.
History of intolerance to any component of the study treatment agents or known serious or severe hypersensitivity reaction to any of the study drugs or their excipients. (Pembrolizumab is formulated with L-histidine, polysorbate 80, and sucrose.

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

313

Study ID:

NCT05070247

Recruitment Status:

Recruiting

Sponsor:

Takeda

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 12 Locations for this study

See Locations Near You

Univeristy of Alabama at Birmingham
Birmingham Alabama, 35294, United States More Info
Site Contact
Contact
919-525-0054
[email protected]
Aakash Desai
Principal Investigator
City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States More Info
Site Contact
Contact
626-256-9200
[email protected]
Vincent Chung
Principal Investigator
University of California San Diego
La Jolla California, 92093, United States More Info
Site Contact
Contact
858-822-5354
[email protected]
Sandep Patel
Principal Investigator
University of Colorado - Anschutz Medical Campus - PPDS
Aurora Colorado, 80045, United States More Info
Site Contact
Contact
303-724-5499
[email protected]
Jennifer Diamond
Principal Investigator
Sarah Cannon Research Institute
Denver Colorado, 80218, United States More Info
Site Contact
Contact
720-754-4653
[email protected]
Jason Henry
Principal Investigator
Sylvester Comprehensive Cancer Center
Miami Florida, 33136, United States More Info
Site Contact
Contact
305-396-8889
[email protected]
Estela Rodriguez
Principal Investigator
Northwestern
Chicago Illinois, 60611, United States More Info
Site Contact
Contact
312-695-6180
[email protected]
Jyoti Patel
Principal Investigator
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Site Contact
Contact
617-632-3000
[email protected]
Harshabad Singh
Principal Investigator
New York University
New York New York, 10016, United States More Info
Site Contact
Contact
212-731-5445
[email protected]
Minas Economides
Principal Investigator
Fox Chase Cancer Center
Philadelphia Pennsylvania, 19111, United States More Info
Site Contact
Contact
215-214-1676
[email protected]
Anthony Olszanski
Principal Investigator
Sarah Cannon Cancer Institute
Nashville Tennessee, 37203, United States More Info
Site Contact
Contact
615-329-7274
[email protected]
Meredith Pelster
Principal Investigator
START South Texas Accelerated Research Therapeutics
San Antonio Texas, 78229, United States More Info
Site Contact
Contact
210-593-5265
[email protected]
Drew Rasco
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

313

Study ID:

NCT05070247

Recruitment Status:

Recruiting

Sponsor:


Takeda

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.

Please confirm you are a US based health care provider:

Yes, I am a health care Provider No, I am not a health care provider