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

Withdrawn

• Conditions: Lymphoma and solid tumors; 10018865; 10027655

• Registration Number: NL-OMON46802
• Lead Sponsor: ovartis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

- ECOG performance status 0 to 2
- Patients progressed after standard therapy or are intolerant of standard therapy or for whom no standard therapy exists
- Measurable disease according to RECIST v1.1 for patients with solid tumors or Cheson criteria for patients with DLBCL
- Patients must have a site of disease amenable for biopsy. On-Treatment biopsy (C1D15) is required for patients with solid tumors
- Histologically or cytologically confirmed diagnosis required for all indications
- Patients with DLBCL: documentation of EZH2 mutational status required in phase II
- Patients with NPC: documentation of presence of p16/CDKN2A gene required
- Patients with ovarian cancer must have a primary tumor wiith great than 50% clear cell histomorphology
- Patients with prostate cancer must have evidence of castration resistance: a confirmed rising PSA and a castrate-serum testosterone level (i.e. * 50 mg/dL);
- Patients with sarcoma: Enrollment is limited to epithelioid sarcoma, other types of sarcoma with SWI/SNF alterations may be considered with approval from Novartis.;Other protocol inclusion criteria may apply (section 5.2)

Exclusion Criteria

- Other malignant disease than the one being treated in this study
- 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.
- B-cell lymphoma patients who have received prior allogeneic stem cell transplant
- Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment (protocol section 5.3 bullet 10)
- CNS involvement which are neurologically unstable or requiring increasing doses of steroids to control.
- 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)
- 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
- 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 (protocol section 5.3)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase 1<br /><br>Safety: DLTs, Incidence and severity of AE's and serious AE's,<br /><br>Tolerability: Dose interruptions, reductions and dose intensity<br /><br><br /><br>Phase 2 : Overall response rate (ORR).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Phase I part<br /><br>Overall Response Rate (ORR), Duration of Overall Response (DOR),<br /><br>Progression-FreeSsurvival PFS) and Best Overall Response (BOR).<br /><br>PK parameters, pre- and posttreatment expression of H3K27 tri methylationin<br /><br>PBsMC<br /><br><br /><br>Phase II part<br /><br>DOR, PFS and BOR<br /><br>Safety: DLTs, Incidence and severity of AE's and serious AE<br /><br>Tolerability: Dose interruptions, reductions and dose intensity<br /><br>PK parameters<br /><br>Pre- and post treatment expression of H3K27 tri methylation in PBMC </p><br>