KRAS G12D

Phase I Study, a master protocol to investigate TCR-Engineered T cells recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.

BDTX-4933-101 is a first-in-human, open-label, Phase 1/2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and/or CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced/metastatic NSCLC with KRAS and/or BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

A first in human study to evaluate the safety and preliminary antitumor activity of BBO-11818, a pan-KRAS inhibitor, in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors.

This is an open-label expanded access protocol (EAP) of ELI-002 7P immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide \[Amph-CpG-7909\] plus a mixture of lipid-conjugated peptide-based antigens \[Amph-Peptides 7P\]) as adjuvant treatment in patients with KRAS/NRAS-mutated pancreatic ductal adenocarcinoma who are at high risk for relapse (ie, presence of isolated tumor cells in a patient whose primary tumor has been removed and is currently without clinical signs of disease). This protocol builds on the experience being obtained with ELI-002 7P (with Amph-Peptides G12D, G12R, G12V, G12A, G12C, G12S, G13D), which is being studied in protocol ELI-002-201.

Recent studies have demonstrated that growth of vascular malformations can be driven by genetic variants in one of 2 signalling pathways. Targeted drugs specific to these pathways have been developed and shown to be effective in treating cancer. This study will describe the effectiveness of (i) 48 weeks of alpelisib therapy for participants with slow-flow vascular malformations and a gene mutation in one of these signalling pathways (module 1) and (ii) 48 weeks of mirdametinib therapy for participants with fast-flow vascular malformations and a gene mutations in the other signalling pathway (module 2).

This is a single-arm, Multicenter, open-label clinical study aimed at evaluating the safety and efficacy of TCR-T injection in patients with advanced solid tumors induced by KRAS mutations.

At present, there is an urgent need for new drugs for KRAS mutant tumors in clinic. Preclinical studies support the specificity, safety and anti-tumor activity of RE002. Previous similar studies suggest the feasibility of TCR-T treatment, and measures have been taken to ensure the safe administration of RE002 and the close monitoring and management of adverse events. To sum up, RE002 has controllable safety and anti-tumor activity on KRAS mutant solid tumor, which can be preliminarily studied to provide support for clinical research of patients with advanced solid tumor.