A safety and efficacy study of MAK683 in adults patients with advanced solid tumors

Phase 1

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

• Registration Number: EUCTR2016-001860-12-IT
• Lead Sponsor: OVARTIS PHARMA SERVICES AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

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

Inclusion Criteria

1. Written informed consent must be obtained prior to any screening procedures
2. Age = 18 years
3. ECOG performance status 0 to 2
4. Patients have progressed after standard therapy or are intolerant of standard therapy and for whom no standard therapy exists.
5. Measurable disease according to RECIST v1.1 for patients with solid tumors or Cheson criteria for patients with NHL (Cheson et al 2014).
6. Tumor biopsy is mandatory at study entry. Patients must have a site of disease amenable for biopsy and be a candidate for tumor biopsy. On-Treatment biopsy is required for patients with solid tumors, unless determined by the Investigator as not clinically feasible.
7. Histologically or cytologically confirmed diagnosis is required for all indications
8. For patients with DLBCL and FL:
- In Phase II, patients are required to have documentation of EZH2 mutational status.
9. 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).
10. For patients with NPC:
- Patients must have documentation of presence of p16/CDKN2A gene (at least one copy of p16/CDKN2A gene)
11. For patients with ovarian cancer:
- Patients must have primary tumor with great than 50% clear cell histomorphology.
12. 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).
13. 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. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 3 years prior to study entry; completely resected basal cell and squamous cell skin cancers; completely resected carcinoma in situ of any type.
2. Symptomatic CNS involvement which are neurologically unstable or require increasing doses of steroids to control.
3. Impaired cardiac function or clinically significant cardiac disease.
4. Current active infection (e.g. viral, bacterial or fungal) requiring systemic therapy.
5. 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.
6. B-cell lymphoma patients who have received prior allogeneic stem cell transplant
7. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal conditions (e.g. atrophic gastritis, peptic ulcer) that might impair the bioavailability of MAK683.
8. Patients with refractory/uncontrolled ascites or pleural effusion.
9. Major surgical procedure within 28 days prior to study treatment.
10. Patients who have received anti-cancer therapies within the following time frames prior to
the first dose of study treatment:
¿ B cell lymphoma patients who received autologous stem cell transplantation within 12
weeks prior to study drug
¿ Castration-Resistant prostate cancer patients who had received radiopharmaceutical agents or immunotherapy (e.g. sipuleucel-T) within 12 weeks prior to study drug
¿ The last dose of conventional cytotoxic chemotherapy: = 4 weeks (= 6 weeks for nitrosoureas and mitomycin-C)
¿ Biologic therapy (e.g., antibodies, CAR-T): = 4 weeks
¿ Non-cytotoxic small molecule therapeutics : = 5 half-lives
11. Any unresolved toxicity NCI CTCAE Grade = 2 from previous anticancer therapy with the exception of alopecia and vitiligo
12. Insufficient bone marrow function at screening:
a) Platelets = 50 x 109/L (50,000/mm3)
b) Hemoglobin (Hgb) = 80 g/L (8 g/dL)
c) Absolute neutrophil count (ANC) = 1.0 x 109/L (1000/mm3)
13. Insufficient hepatic and renal function at screening:
a) Alkaline phosphatase (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) more than or equal to 3 x ULN (more than or equal to 5 x ULN if subject has liver metastases)
b) Total bilirubin > 1.5 x ULN.
c) Serum creatinine > 1.5 x ULN and/or creatinine clearance = 50 mL/min (calculated
using Cockcroft-Gault formula
14. Concomitant use of the drugs/remedies that may cause pharmacokinetic drug-drug interactions.
15. Chronic steroid therapy other than following: Daily use 10 mg prednisone (or equivalent)
or lower dose steroid for control of nausea, vomiting, active autoimmune disease, and
seasonal allergies, or to prevent adrenocortical insufficiency. NOTE: topical steroid, or inhaled steroid use is permitted.
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
17. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 4 weeks after discontinuation of treatment.
18. Sexually active males unless they use a condom d

Study & Design

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