A Phase 1/2 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, and Pharmacokinetics of TAK-981 in Adult Patients With Solid Tumors or Hematologic Malignancies

Phase 1

• Conditions: Advanced or Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies; MedDRA version: 21.1Level: LLTClassification code 10066481Term: Hematological malignancySystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-003947-27-BE
• Lead Sponsor: Takeda Development Center Americas, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-15
• Last Update Posted: 9 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

1. Adult male or female patients =18 years old.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
3. Patient population for Phase 1 dose escalation:
a. Have a histologically or cytologically confirmed advanced or metastatic solid tumors who have no standard therapeutic option with a proven clinical benefit, are intolerant, or have refused them.
b. Have a relapsed/refractory lymphoma not amenable to therapies with proven clinical benefit or who are intolerant or who refuse them. Patients with low-grade lymphomas such as FL, small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, and marginal zone lymphomas may not need to exhaust all available therapy. These patients can be enrolled after failure of at least 2 prior systemic therapies, provided that there is not an immediate need for cytoreduction. In these cases, patients who need immediate therapy for tumor bulk are not eligible for this trial.
4. Patient population for Phase 2 dose expansion cohorts:
Have a histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below, which is incurable and for which prior standard first-line treatment has failed:
a.Nonsquamous NSCLC that has progressed to 1 prior systemic immune checkpoint inhibitor (CPI)/anti-PD-(1/L1)-containing therapy and no more than 2 lines of therapy. Patients must have not shown evidence of tumor progression during the first 5 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy (cohort A).
b. CPI-naïve cervical cancer (squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix) patients who have received no more than 1 prior systemic line of therapy for recurrent or Stage IVB cervical cancer (cohort B).
c. CPI-naïve MSS-CRC patients who have progressed on no more than 3 chemotherapy regimens (cohort C).
d. Relapsed/refractory DLBCL progressed or relapsed after a prior CAR T-cell therapy that has received approval by a health authority for the treatment of DLBCL (Cohort D).
e. Relapsed/refractory DLBCL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy and has not received prior cellular therapy. At least one prior line of therapy must have included a CD20-targeted therapy (cohort E).
f. Relapsed/refractory FL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy. At least one prior line of therapy must have included a CD20-targeted therapy (cohort F).
5. In Phase 2 only, have at least 1 radiologically measurable lesion based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for patients with solid tumors or Lugano criteria for lymphoma. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. In Phase 2 stage 1, willing to consent to mandatory pretreatment and on-treatment tumor biopsy.
7. Is willing to provide archival tumor tissue sample, if available.
8. Adequate bone marrow reserve and renal and hepatic function based on the following laboratory parameters:
a. Absolute neutrophil count (ANC) =1.0 × 109/L, hemoglobin =85 g/L (red blood cell transfusion allowed =14 days before assessment), and platelet count =75.0 × 109/L(platelet count =50.0 × 109/L is allowed for patients with lymphoma if it is clearly due to marrow involvement with no evidence of myelodysplastic syndrome or hypoplastic bone marrow, if found

Exclusion Criteria

1. Phase 1 dose escalation and Phase 2 cancer treatment expansion cohorts:
a. Have received treatment with systemic anticancer treatments or investigational products within 14 days before the first dose of study drug or 5 half-lives, whichever is shorter.
b. Have received extended field radiotherapy =4 weeks before the start of treatment (=2 weeks for limited field radiation for palliation) and have not recovered to Grade 1 or baseline from related side effects of such therapy (except for alopecia).
2. Have a history of uncontrolled brain metastasis. Patients with brain metastases are allowed if they are previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery and the patients are receiving a corticosteroid dose =10 mg/day of prednisone equivalent at the time of receiving the first dose of TAK-981. For asymptomatic patients, screening brain imaging is not required.
3. Patient is receiving any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
4. History of any of the following =6 months before first dose: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, severe noncompensated hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias of >Grade 2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
5. Baseline prolongation of the QT interval with Fridericia correction method (QTcF) (eg, repeated demonstration of QTcF interval >480 ms, history of congenital long QT syndrome, or torsades de pointes).
6. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent.
7. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
8. History of autoimmune disease requiring systemic immunosuppressive therapy with daily doses of prednisone >10 mg/day or equivalent doses, or any other form of immunosuppressive therapy. Hormone therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered an excluded form of systemic treatment of an autoimmune disease
9. History of immune-related AEs related to treatment with immune checkpoint inhibitors that required treatment discontinuation.
10. History of noninfectious pneumonitis that required steroids or a history of interstitial lung disease.
11. Has evidence of active, noninfectious pneumonitis.
12. Have a significant active infection.
13. Known history of human immunodeficiency virus infection or any other relevant congenital or acquired immunodeficiency.
14. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C infection viral load.
15. Receiving or requiring the continued use of medications that are known to be strong or moderate inhibitors and inducers of CYP3A4/5 or are strong P-gp inhibitors at screening. To participate in this study, such patients should discontinue use of such agents for at least 2 weeks (1 week for CUP3A4/5 and P-gp inhibitors) before receiving a dose of TAK-981.
16. Patient requires the use of drugs known to prolong QTc interval (during Phase 1 only)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified