A Study of TAK-676 and TAK-676 in Combination With Pembrolizumab in Adults With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2023-03-11
• Target enrollment: 0
• Participant gender: All

Summary

It is hoped that TAK-676, when given on its own or given with pembrolizumab will eventually help people with advanced or metastatic solid tumors.

The main aim of this study is to check if people with advanced solid tumors have side effects from TAK-676, and to check how much TAK-676 they can receive without getting side effects from it.

At the first visit, the study doctor will check who can take part. Participants will receive TAK-676 slowly through a vein (infusion). This will happen on 3 different days during a 21-day cycle. Different small groups of participants will receive lower to higher doses of TAK-676. Some participants will receive TAK-676 by itself and others will receive TAK-676 with pembrolizumab.

Participants will stay in the clinic or hospital for 24 hours after each infusion of TAK-676 in the first cycle of treatment. Sometimes the study doctor will carry out a physical exam before the participant goes home. Participants will be given an emergency card to carry with them at all times. The card has information about the study including contact details and a 24-hour emergency number.

Some participants, who receive TAK-676 and are willing and able, will be asked to wear a removable patch on their chest to record vital signs for 21 days in the first cycle of treatment. Also, in the first cycle of treatment, participants will record their oral temperatures twice a day for 21 days in a diary when they go home after each infusion.

Throughout treatment, the clinic will regularly telephone the participants to check on their health.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Millennium Pharmaceuticals, Inc.; Takeda
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

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

2. Life expectancy >12 weeks, as assessed by the investigator.

3. TAK-676 SA:

o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to these therapies.

4. TAK-676 in combination with pembrolizumab:

o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to them, including:

• Tumors that have relapsed or are refractory to anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed cell death ligand 1 (anti-PD-L1) therapy.

• Tumors that are naive to anti-PD-1/ anti-PD-L1 therapy.

5. Adequate bone marrow, renal, hepatic and cardiac functions.

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

7. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy.

8. Once peripheral evidence of TAK-676 pharmacodynamic stimulation of the innate and/or adaptive immune system is observed in the blood and/or clinical response/partial response (CR/PR) is observed in at least 1 participant, subsequent participants must:

• Have at least 1 lesion amenable for biopsy.

• Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on TAK-676 treatment.

9. Must have at least 1 RECIST v.1.1-evaluable (measurable or nonmeasurable) lesion.

10. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-inserted catheter. TAK-676 is preferentially administered through a central line, but peripheral infusion is acceptable. If a peripheral line is used for TAK-676 and/or pembrolizumab infusion, it must be separate than the one used for PK/ pharmacodynamic collection.

Exclusion Criteria:

1. Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men) or >475 milliseconds (women) on a 12-lead ECG during the screening period.

2. Grade greater than or equal to (>=) 2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 predose assessment.

3. Oxygen saturation less than (<) 92 percent (%) on room air at screening or during C1D1 predose assessment.

4. Treated with other STING agonists/antagonist and toll-like receptors agonists within the past 6 months.

5. Active vaping within 90 days of C1D1 of study drug(s).

6. Active smoking.

7. Current history 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 or ascites not controlled by tap or requiring indwelling catheters.

8. History of brain metastasis unless:

• Clinically stable (that is, >=6 weeks) following prior surgery, whole-brain radiation, or stereotactic radiosurgery, AND

• Off corticosteroids.

9. Ongoing Grade >= 2 infection or participants with Grade >=2 fever of malignant origin.

10. Chronic, active hepatitis (example: participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA).

11. For participants in the SA arm only: refusal of standard therapeutic options.

12. For participants in the combination arm only: contraindication and/or intolerance to the administration of pembrolizumab.

13. Concurrent chemotherapy, immunotherapy (except for pembrolizumab in the combination arm), biologic, or hormonal therapy (except for adjuvant endocrine therapy for a history of breast cancer). Concurrent use of hormones for noncancer-related conditions is acceptable (except for corticosteroid hormones).

14. 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.

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

• Topical, intranasal, inhaled, ocular, and/or intra-articular corticosteroids.

• Physiological doses of replacement steroid therapy (example: for adrenal insufficiency).

16. Use of medications that are known clinical OATP1B1 and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study drug(s).

17. Receipt of live attenuated vaccine within 28 days of C1D1 of study drug(s).

18. Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.