Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

Phase 1

Terminated

• Conditions: Diffuse Large B-cell Lymphoma
• Interventions: Drug: MAK683

• Registration Number: NCT02900651
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of this Phase I/II study is to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and to evaluate the safety, antitumor activity and pharmacokinetic (PK) profile of MAK683 in patients with advanced malignancies such as Diffuse Large B cell Lymphoma (DLBCL), nasopharyngeal carcinoma (NPC) or other advanced solid tumors for whom no further effective standard treatment is available.

Detailed Description

The purpose phase I of this trial is to characterize safety and tolerability and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of MAK683.

The purpose of the phase II of this trial is to evaluate the anti-tumor activity of MAK683. Phase II part will not be opened.

Study Timeline

• Study First Submitted: 2016-09-02
• Study First Submitted QC: 2016-09-09
• Study First Posted: 2016-09-14
• Study Start: 2016-10-03
• Status Verified: 2024-10
• Primary Completion: 2024-10-09
• Study Completion: 2024-10-09
• Last Update Submitted: 2024-10-29
• Last Update Posted: 2024-10-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 139

Inclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG): 0 to 2
2. Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014)
3. Advanced or recurrent/metastatic solid tumor, including nasopharyngeal carcinoma, castration-resistant prostate cancer, gastric cancer, ovarian clear cell carcinoma and sarcoma, with measurable disease as determined by RECIST 1.1.

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Exclusion Criteria

1. Other malignant diseases than the ones being treated in this study
2. Severe and/or uncontrolled medical conditions that in the investigator's opinion could affect the safety of individual or impair the assessment of study result.
3. B-cell lymphoma patients who have received prior allogeneic stem cell transplant
4. Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment
5. Symptomatic central nervous system (CNS) involvement which are neurologically unstable or requiring increasing doses of steroids to control.
6. Patient having out of range laboratory values defined as:

1. Insufficient bone marrow function at screening:

• Platelets ≤ 50,000/mm3
• Hemoglobin (Hgb) ≤ 80 g/L
• Absolute neutrophil count (ANC) ≤ 1000/mm3 2) Insufficient hepatic and renal function at screening:
• ALP, ALT, and AST > 3 x ULN (>5 x ULN if subject has liver metastases)
• Total bilirubin >1.5 x ULN
• Serum creatinine > 1.5 x ULN and/or creatinine clearance ≤ 50 mL/min

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase I - All	MAK683	advanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma.

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities (DLTs)	up to 28 days	Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety and tolerability	up to approximately 3 years	Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration (AUC) Time Curve of MAK683	30 months	Pharmacokinetic profile of MAK683
Half-Life of MAK683	30 months	Pharmacokinetic profile of MAK683
Overall Response Rate (ORR)	up to 30 months
Peak Plasma Concentration (Cmax) of MAK683	30 months	Pharmacokinetic profile of MAK683
H3K27 tri methylation level in PBMC	up to day 15	Cycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cell
Duration of overall response (DOR)	up to 30 months
Best Overall Response (BOR)	up to 30 months
Progression-free survival (PFS)	up to 30 months

Trial Locations

Locations (4)

Uni Of TX MD Anderson Cancer Cntr Dept of Onc; 🇺🇸 Houston, Texas, United States

UCSF .; 🇺🇸 San Francisco, California, United States

UCLA Santa Monica Hematology Oncology; 🇺🇸 Santa Monica, California, United States

Novartis Investigative Site; 🇪🇸 Madrid, Spain