A phase I/II, multicenter, open-label study of MAK683 in adult patients with advanced malignancies

Phase 1

• Conditions: MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864; Advanced malignancies; MedDRA version: 21.1Level: LLTClassification code 10066481Term: Hematological malignancySystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001860-12-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-09-15
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

1.Patients Age = 18 years
2.ECOG performance status 0 to 2
3.Patients have progressed after standard therapy or are intolerant of standard therapy and for whom no standard therapy exists.
4. Measurable disease according to RECIST v1.1 for patients with solid tumors or Cheson criteria for patients with NHL (Cheson et al 2014).
5. Tumor biopsy is mandatory at study entry. Patients must have a site of disease amenable for biopsy and be a candidate for umor biopsy. On-Treatment biopsy is required for patients with solid tumors, unless determined by the Investigator as not
clinically feasible.
6. Histologically or cytologically confirmed diagnosis is required for all indications
- For patients with DLBCL and FL: In Phase II, patients are required to have documentation of EZH2 mutational status.
Patients with relapsed or refractory indolent lymphomas, such as FL, must have signs or symptoms indicating the necessity of therapy such as described in practice guidelines ( e.g. Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, The British National Lymphoma Investigation (BNLI), Italian Society of Hematology (SIE) guideline, or others
local practice guidelines).
7. For patients with NPC: Patients must have documentation of presence of p16/CDKN2A gene (at least one copy of p16/CDKN2A gene)
8. For patients with ovarian cancer: Patients must have primary tumor with great than 50% clear cell histomorphology.
9. For patients with prostate cancer: Patients must have evidence of castration resistance as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a castrate^serum testosterone level (i.e. = 50 ng/dL).
10. For patients with sarcoma: Enrollment is limited to epithelioid sarcoma, other types of sarcoma with SWI/SNF alterations may be considered with approval from Novartis.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1.Other malignant disease than the one 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 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 x 109/L (50,000/mm3)
•Hemoglobin (Hgb) = 90 g/L (9 g/dL)
•Absolute neutrophil count (ANC) = 1.0 x 109/L (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 =2 x ULN
•Serum creatinine > 1.5 x ULN and/or creatinine clearance = 50 mL/min
7.Unable to stop any prohibited medications, including strong CYP3A4 inhibitors or inducers, CYP3A4 or CYP2C8 substrates with a narrow therapeutic index, long acting proton pump inhibitors.
Other protocol-defined exclusion criteria may apply.

Study & Design

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