A phase I dose finding study of oral LXH254 in adult patients with advanced solid tumors harboring MAPK pathway alterations.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

** 18 years old.
*Progressed following standard therapy, or, in the opinion of the Investigator,
no effective standard therapy exists, is tolerated or appropriate.
*Dose escalation part: Advanced solid tumors, harboring at least one MAPK
pathway alteration (see protocol Table 5-1) when enrolled in cohorts testing
LXH254 single agent or NSCLC patients and NRAS mutant melanoma patients with
specific mutations in the MAPK pathways for cohorts testing LXH254 in
combination with PDR001.
*Dose expansion part: other advanced solid tumors harboring documented MAPK
pathway alteration (protocol Table 5-1). These include but are not limited to:
-Confirmed KRAS and/or BRAF-mutated NSCLC.
-Confirmed KRAS and/or BRAF-mutated ovarian cancer.
-BRAF V600-mutated melanoma patients who are refractory to or relapsed on
prior BRAFi/MEKi combination therapy, NRAS-mutated melanoma
LXH254 in combination with PDR001: NSCLC patients with specific mutations in
the MAPK pathway and patients with NRAS mutated melanoma
-NRAS- mutated solid tumors,
*ECOG performance status 0-1

Exclusion Criteria

*Prior treatment with a BRAF, MEK and/or pan-RAF inhibitor in patients with
confirmed KRAS and/or BRAF-mutated NSCLC and ovarian cancer in dose expansion
part.
*Prior treatment with any of the following (see protocol page 37 for details
incl. time frames): radiation, chemotherapy, cytotoxic agents with major
delayed toxicities, major surgery, immunotherapy.
*History or current evidence of retinal vein occlusion (RVO) or current risk
factors for RVO.
*Gilbert*s syndrome or other heritable diseases of bile processing.
*Clinically significant cardiac disease, see protocol page 38 for details.
*Out of range laboratory values. See protocol page 38-39 for details.
*Sexually active males unless they use a condom during intercourse.
*Pregnancy, lactation, insufficient contraception for females of childbearing
potential.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Adverse events, DLTs.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Overall response rate, disease control rate, progression free survival,<br /><br>duration of response, overall survival. PK parameters of LXH254 and PDR001.<br /><br>DUSP6 (as PD marker) for LXH254, Emergence of anti-PDR001 antibodies: Presence<br /><br>and/or concentration of anti-PDR001 antibodies. BA of a new LXH254 tablet<br /><br>formulation compared to the current LXH254 formulation </p><br>