A phase I dose finding study of oral LTT462 in adult patients with advanced solid tumors harboring MAPK pathway alterations - A phase I study with LTT462 in tumors with MAPK pathway alterations

ovartis0 个研究点目标入组 6 人开始时间: 待定最近更新: 2024年4月23日

适应症

试验速览

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•1. >=12 years of age (in Netherlands: >=18 years of age)
•2. Must have progressed following standard therapy, or, in the opinion of the Investigator, no effective, tolerated or appropriate standard therapy.
•3. ECOG performance status 0, 1.
•4. Presence of at least one measurable lesion (RECIST v1.1).
•5. Archival tumor tissue or fresh tumor tissue at screening.
•6. Patients must be willing to undergo study required biopsies.;Dose escalation part:
•Advanced solid tumors harboring at least one of the MAPK pathway alterations.;Dose expansion part:
•Group 1: confirmed KRAS and/or BRAF-mutated NSCLC.
•Group 2: confirmed KRAS and/or BRAF-mutated ovarian cancer.
•Group 3: BRAFV600 mutated melanoma. Initial response to, or stable disease for at least 6 months on a BRAFi and/or MEKi but then relapse. BRAFi and/or MEKi as the last line of treatment prior to entry into the study, or only one immunotherapy agent (e.g. anti-CTLA-4, anti PD-1, anti-PD-L1) following BRAFi and/or MEKi failure.
•Group 4: other advanced solid tumors harboring documented MAPK pathway alteration(s) other than those defined in Group 1, 2 and 3. ;Other criteria may apply. See protocol page 39-40 for more details.

•1. Prior treatment with ERK inhibitors.
•2. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
•3. Other severe, acute or chronic medical condition that prevent the patient*s participation in the clinical study due to safety concerns
•4. Treatment with strong inhibitors and/or inducers of CYP3A and CYP2C8; substrates of CYP3A with a narrow therapeutic index; and sensitive substrates of CYP3A, which cannot be discontinued 7 days prior to the start study treatment.
•5. Proton pump inhibitors which cannot be discontinued 3 days prior to the start of study treatment.
•6. Clinically significant cardiac disease.
•7. Insufficient bone marrow function at screening: Absolute Neutrophil Count (ANC) < 1.5 x 109/L, Hemoglobin (Hgb) < 9.0 g/dL, Platelets < 75 x 109/L
•8. Insufficient hepatic and renal function at screening: total bilirubin > 1.5 x upper limit of normal (ULN), AST or ALT > 3 x ULN or > 5.0 x ULN if liver metastases are present, creatinine > 1.5 x ULN
•9. Pregnancy, lactation, insufficient contraception for females of childbearing potential.;Other criteria may apply. See protocol page 40-43 for more details.

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