This first-in-human (FIH) study aims to assess the safety, tolerability, pharmacokinetics, and recommended phase 2 dose (RP2D) of D3S-002 given orally daily for 21-day cycles in adult subjects with advanced solid tumors with mitogen-activated protein kinase (MAPK) pathway mutations.
Part 1: Subjects must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor with evidence of progressive disease.
Part 2: Subjects must have a histologically or cytologically confirmed metastatic or locally advanced non-small cell lung cancer with evidence of PD.
Subjects with non-small cell lung cancer (NSCLC) should have no known epidermal growth factor receptor (EGFR) mutations, ALK/ROS1/RET rearrangements, NTRK1/2/3 gene fusions, v-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations, or MET exon 14 skipping mutations.
Part1: Subjects must have documented mitogen-activated protein kinase (MAPK) pathway mutation(s) within the last 5 years identified by a local test on tumor tissue or blood (eg, rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), and MAPK kinase (MAPKK) mutations).
Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol.
Part 2: subjects with mixed small-cell lung cancer, or large cell neuroendocrine histology, or sarcomatoid carcinoma.
Subject has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent.
Part 1: Uncontrolled or untreated brain metastasis.