Sufficient exposure to RMC-4630 and LY3214996 was not reached due to the toxicity profile of the combination. Tumor response was not demonstrated at the explored dose levels. Therefore, the dose escalation was discontinued, and the RP2D was not determined.

P1/2, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=46 --> 12

P1, N=90, Active, not recruiting, Erasca, Inc. | N=200 --> 90 | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: Nov 2025 --> Feb 2026

P1/2, N=152, Not yet recruiting, Suzhou Genhouse Bio Co., Ltd.

In a murine model of MDA-MB-231-induced osteolytic lesions, oral administration of 10 mg/kg SHP099 reduces osteoclasts and prevents the trabecular bone loss. Our study identifies SHP2 as a druggable target for inhibiting breast cancer-induced osteoclast differentiation, positioning the specific inhibitors of SHP2 as potential drugs developed to treat tumour-induced osteolysis in the future.

Regimens co-targeting the MAPK pathway and ALK or ROS1 had limited efficacy in unselected patients with lorlatinib-resistant NSCLC, underscoring the need for more effective and biomarker-informed treatment strategies.

Notably, the combination of LPM5140276 and RMC4550 synergistically suppressed ERK and SHP2 phosphorylation, enhanced G0/G1 arrest and apoptosis, and improved the antitumor efficacy. Thus, LPM5140276 is a promising KRASG12D inhibitor, whose combination with SHP2 inhibition represents a viable strategy for overcoming resistance.

P1/2, N=46, Recruiting, Memorial Sloan Kettering Cancer Center | N=11 --> 46

P2, N=120, Not yet recruiting, Suzhou Genhouse Bio Co., Ltd.

P1, N=40, Completed, Jacobio Pharmaceuticals Co., Ltd. | Recruiting --> Completed | N=24 --> 40

Glecirasib combined with sitneprotafib showed promising efficacy and manageable safety in patients with advanced KRASG12C -mutated NSCLC, particularly among those who had not received previous treatment. These findings support the evaluation of this combination in a phase 3 trial comparing this chemotherapy-free regimen to current standard of care in this patient group.

G-LNP@S-D consists of GM1-functionalized liposomes co-encapsulating the SHP2 inhibitor SHP099 and the STING agonist DMXAA, enabling sequential lymph node- and CD169+ macrophage-specific drug delivery...Importantly, G-LNP@S-D exerts systemic immunomodulatory effects for directly eradicating lymphatic metastases. This study elucidates a sophisticated lymph node immune-modulation strategy and provides a promising therapeutic approach to treat lymphatic metastasis.