Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety, tolerability, and preliminary clinical activity of Tulmimetostat as a monotherapy in patients with advanced solid tumors and lymphomas.
Full description
The study is divided into Phase 1 and Phase 2. In Phase 1 and the Phase 2 expansion (M1 to M7), patients are non-randomized. In Phase 2 optimization, patients in Cohort M2 and M3 (Stage 2a and 2b) and Cohort M8 (Part 2) are randomized.
Phase 1 of the study is composed of a Tulmimetostat Dose Escalation period in patients with advanced tumors and aims to determine maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of Tulmimetostat as monotherapy in patients with advanced tumors.
Phase 2 of the study is planned to evaluate safety and tolerability and antitumor activity of Tulmimetostat in six disease-specific cohorts (M1 to M6). Patients in Cohorts M1, M2, M3, M5, and M6 will be enrolled at 10 to 29 patients per cohort, using a Simon 2-stage design. Cohort M4 will enroll up to 20 patients with lymphoma in a single-stage.
The primary aim of Phase 2 part of the study is to evaluate the antitumor activity of Tulmimetostat, and characterize the safety and tolerability of Tulmimetostat as monotherapy in patients with selected tumors.
In Phase 2, two additional doses are planned to be evaluated in cohorts M2 and M3 in 2 stages: Stage 2a and Stage 2b. In Stage 2a approximately 20 patients will be enrolled per cohort and will be randomized 1:1 to receive 2 prespecified dose levels of Tulmimetostat once daily. When protocol criteria for initiating Stage 2b will be fulfilled after completion of Stage 2a, then Stage 2b will be opened for enrolment of additional 10 patients in one or both dose arms in each of the two cohorts. Thus, up to 40 patients per cohort (M2 and M3) could be enrolled.
The study will explore the Tulmimetostat in anti-tumor activity and effect of food on pharmacokinetics of Tulmimetostat in in patients with ARID1A WT endometrial carcinoma (Cohort M7) and safety and anti-tumor activity of Tulmimetostat in in combination with enzalutamide in patients with mCRPC (Cohort M8).
In Cohort M8 Part 1, the safety and tolerability of Tulmimetostat in and enzalutamide combination will be evaluated in patients with mCRPC. The M8 Part 1 dose escalation incorporates combination of Tulmimetostat in at escalating provisional doses with enzalutamide.
In Cohort M8 Part 2, the safety, tolerability and preliminary antitumor activity of Tulmimetostat at a RP2D in combination with enzalutamide will be further evaluated in patients with mCRPC.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Key Inclusion Criteria:
Key Exclusion Criteria:
Medical Conditions
Previous solid organ or allogeneic hematopoietic cell transplantation (HCT).
Known symptomatic untreated brain metastases. Patients with central nervous system (CNS) metastases must have stable neurologic status following local therapy for at least 4 weeks on a stable or decreasing dose of steroids (≤ 10 mg daily prednisone or equivalent). Patients in the M4 lymphoma cohort are excluded if they have known CNS involvement by lymphoma.
Clinically significant cardiovascular disease, including:
Major surgery within 4 weeks before starting study drug or not recovered from any effects of prior major surgery (uncomplicated central line placement or fine needle aspirate are not considered major surgery).
Gastrointestinal disorders that may significantly interfere with the absorption of the study medication, such as ulcerative colitis, malabsorption syndrome, refractory nausea and vomiting, biliary shunt, significant bowel resection.
Uncontrolled active infection requiring intravenous antibiotic, antiviral, or antifungal medications within 14 days before the first dose of study drug. Controlled infections on concurrent antimicrobial agents and antimicrobial prophylaxis per institutional guidelines are acceptable.
Suspected pneumonitis or interstitial lung disease (confirmed by radiography or CT) or a history of these conditions.
History of a concurrent or second malignancy except for certain adequately treated cancers such as local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer in complete remission for ≥ 3 years. Patients with a history of T-cell lymphoblastic lymphoma or T-cell lymphoblastic leukemia are not eligible.
Current known active or chronic infection with HIV, hepatitis B, or hepatitis C. Screening for these viruses is not required unless there is a past history or current suspicion of viral hepatitis.
Clinically active or symptomatic viral hepatitis or chronic liver disease.
Unstable or severe uncontrolled medical condition or any important medical or psychiatric illness or abnormal laboratory finding that would increase the risk to the patient associated with participation in the study.
For Cohort M7 Only: Patients not willing to or cannot remain fasted due to a medical condition for 2 hours before and 1 hour after dose administration.
Prior/Concomitant Therapy:
Prior Anticancer Treatment:
Concomitant Medication:
Other Exclusions
General Exclusions:
Additional Exclusions for Cohort M6 (mCRPC) Only:
Bone-only Disease: Patients with bone-only disease without nodal disease and no evidence of visceral spread are excluded.
Structurally Unstable Bone Lesions: Patients with bone lesions that are structurally unstable and concerning for impending fracture are excluded.
Herbal Products: Patients using herbal products that may decrease prostate-specific antigen (PSA) levels within 4 weeks prior to Day 1 of treatment and during the study are excluded.
Prostate Cancer Treatments: Patients who have received the following treatments for prostate cancer within the specified timeframes prior to Day 1 of treatment are excluded:
Planned Palliative Procedures: Patients with planned palliative procedures for alleviation of bone pain, such as radiation therapy or surgery, are excluded.
Additional Exclusion Criteria for Cohort M8 (DZR123 and Enzalutamide Combination in mCRPC) only:
Biochemical recurrence/prostate-specific antigen (PSA)-only disease.
Prior Enzalutamide Treatment:
Herbal Products: Use of herbal products that may decrease PSA levels within 4 weeks prior to Day 1 of treatment and during the study.
Planned Palliative Procedures: Planned palliative procedures for alleviation of bone pain, such as radiation therapy or surgery.
Investigational Agents: Treatment with any investigational agent within 4 weeks before Day 1 of M8 Part 1 or M8 Part 2.
Bone Marrow Irradiation: Prior irradiation to more than 25% of the bone marrow.
Gastrointestinal Conditions: Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease, or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
Seizure History: History of seizure, loss of consciousness, or transient ischemic attack within 12 months of study entry, or any condition that may predispose to seizure (e.g., stroke, brain arteriovenous malformation, head trauma, underlying brain injury).
Primary purpose
Allocation
Interventional model
Masking
275 participants in 10 patient groups
Loading...
Central trial contact
Novartis Pharmaceuticals; Novartis Pharmaceuticals
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal