A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations

Inclusion Criteria

• •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.
• •Note: EGFR mutations include but are not limited to EGFR Exon19 Deletions, Exon21 p.L858R, Exon21 p.L861Q, Exon18 p.G719X, Exon20 p.S768I, Exon20 Insertions, Exon20 p.T790M. If other EGFR mutations are present, the Investigator should have a consultation with the sponsor's Medical Monitor before making the enrollment decision.
• •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).
• •Part 2: Subject must have documented Kirsten rat sarcoma viral oncogene (KRAS) p. glycine 12 to cysteine (p.G12C) mutation identified within the last 5 years by a local test on tumor tissue or blood.
• •Note:
• •All the local tests should clearly distinguish KRAS p.G12C from all other KRAS p.G12x variants. If not specified, subjects should have no known second KRAS mutations (including G12A, G12V, G12R, G13C, G12D, G12S, H95, Y96, Q61, and R68).
• •Part 1: Subjects must be refractory to or intolerable with standard treatment, or have no available standard of care (SOC).
• •Part 2: Subject must have received at least 1 line of prior standard of care systemic therapy for locally advanced and unresectable or metastatic disease, including KRAS p.G12C inhibitor.
• •Note:
• •Subjects should only have received 1 type of prior KRAS p.G12Ci treatment (including all types of KRAS p.G12C inhibitor which are either under investigation or in market, except D3S-001).
• •During the prior KRAS p.G12C treatment, subject has achieved best response of partial or complete response regardless of KRAS p.G12Ci treatment duration, or stable disease for at least 6 months. However, subjects, who have stopped KRAS p.G12Ci therapy earlier than 6 months due to safety/tolerability reasons only, would be allowed. In such a situation, the Investigator should have a consultation with the Sponsor Medical Monitor before making the enrollment decision.
• •* Part 2: Subjects must have measurable disease per RECIST v1.1.
• •* Part 2: Subjects must agree to provide archival tumor tissue, if available, for genetic analysis. If archival tumor tissue is not available, or of insufficient quantity, an optional fresh biopsy is highly recommended.
• •* Part 2: Subjects must agree to provide blood samples for genetic analysis (Table 2 schedule of activities for Part 2).
• •* Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• •* Subject must have adequate organ and marrow function within the screening period.
• •* Subjects must comply with all reproductive and contraceptive requirements outlined in the protocol.