NXP900 / Nuvectis Pharma - LARVOL DELTA

First-in-class switch-control SRC/YES1 inhibitor NXP900 demonstrates potent synergy with KRAS inhibitors in drug-sensitive and resistant NSCLC models in vitro and in vivo (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Study of NXP900 With Lorlatinib in ALK+ Lung Cancer (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Nuvectis Pharma, Inc.

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

The c-Src inhibitor eCF506 diminishes opioid tolerance and reduces β-arrestin2 recruitment. (PubMed, Br J Pharmacol) - "These findings suggest that selective inhibition of c-Src by eCF506 prolongs opioid antinociception by limiting β-arrestin2-dependent regulation and trafficking of μ receptors, while preserving G-protein signalling, identifying c-Src as a mechanistically distinct target for modulating opioid tolerance."

Journal • Addiction (Opioid and Alcohol) • Pain • ARRB1

Targeting SRC/YES1 with the novel oral molecule NXP900 delays Osteosarcoma tumor growth and metastatic dissemination (EACR 2026) - "Unlike conventional SRC inhibitors such as dasatinib or bosutinib, which act as multi-tyrosine kinase inhibitors targeting SRC catalytic activity, NXP900 stabilizes SRC in its inactive closed conformation, thereby suppressing both kinase and scaffolding functions. These data provide preclinical proof of principle supporting the therapeutic potential of NXP900 in OS, demonstrating both direct antitumor activity and modulation of tumor-promoting signaling pathways. SRC inhibition therefore represents a promising targeted therapeutic strategy for this aggressive paediatric tumor."

Metastases • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Inhibition of SRC prevents bone metastasis of breast cancer by blocking metastatic cell motility and bone directionality. (PubMed, Theranostics) - "SRC inhibition also attenuated immune evasion, enhanced anti-tumor immunity, and synergized with anti-PD-1 or gemcitabine/bisphosphonate therapies...This study demonstrates that SRC plays distinct and essential roles in cancer cell motility, osteoclast activation, and immune evasion, which collectively drive breast cancer bone metastasis. These findings establish SRC as a critical therapeutic target and suggest that dual inhibition of its kinase and scaffolding functions represents a more effective strategy than conventional approaches."

Journal • Breast Cancer • Oncology • Solid Tumor

Resistance to the SFK inhibitor NXP900 in cholangiocarcinoma is characterized by IL13RA2-AKT signaling and can be overcome by combination therapy (AACR 2026) - "NXP900 is a highly selective SFK inhibitor with a novel mechanism of action that locks SFKs in a closed, inhibited conformation, providing sustained suppression of catalytic and non-catalytic functions, which is distinct from other SFK inhibitors like dasatinib. These findings confirm the central role of IL13RA2 signaling and the PI3K-AKT pathway in mediating acquired resistance to NXP900, consistent with our previous multiomics analysis. Importantly, this study identifies combination strategies that may be able to overcome NXP900 resistance, supporting the development of combinatorial approaches to restore therapeutic efficacy in resistant tumors."

Combination therapy • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IL13RA2

NXP900, a Phase 1b, first-in-class YES1/SRC inhibitor demonstrates potent synergy with KRAS inhibitors in KRASi sensitive and resistant NSCLC models (AACR 2026) - P1 | "Moreover, no CYP3A induction was observed in a drug-drug interaction study in humans indicating the potential of NXP900 to be combined with KRASi to overcome primary and acquired resistance and improve clinical benefit to patients with KRAS mutated cancers.Materials and Resistant cell lines to the KRASi sotorasib were generated from NCI-H23 cells.Cell proliferation assay - Cells were diluted in the corresponding ATCC recommended medium and dispensed in a 384-well plate, depending on the cell line used, at a density of 100 - 6400 cells per well. Development of effective and tolerable combination therapies are needed to overcome resistance and maximize the clinical impact of RAS-targeted therapy. NXP900 can potently inhibit cell proliferation of KRAS mutated cell lines in combination with a KRASi in NSCLC models. The combination was synergistic both in KRAS sensitive and resistant models."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FAT1 • KRAS • LATS1 • YAP1

Targeting myeloid-derived suppressor cells (MDSCs) to restore antitumor immunity in non-small cell lung cancer (NSCLC) via SRC family kinase Inhibition with NXP900 (AACR 2026) - P1 | "These findings identify MDSCs as a key immunosuppressive driver of prognostic significance in NSCLC. NXP900 currently in a Phase 1b study (NCT05873686) including in NSCLC patients with YES1 and FAT1 genomic alterations, effectively suppresses MDSC viability and YAP1 signaling in vitro, supporting its potential as a novel therapy in NSCLC."

Myeloid-derived suppressor cells • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD14 • CD20 • CD8 • FAT1 • ITGAM • NF2 • YAP1

NXP900, a novel YES1/SRC kinase inhibitor in phase 1, demonstrates potent inhibition of proliferation in cell lines resistant to ALK and EGFR inhibitors (AACR 2024) - "In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active "open" conformation (type 1) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Despite high response rates to osimertinib and alectinib, acquired resistance almost universally arises. Here we demonstrate that NXP900 can potently inhibit cell proliferation of ALK resistant cell lines as a single agent and EGFR resistant cell lines in combination with osimertinib. Activation of SFK and YAP1 has been shown to be important in the development of resistance to ALK and EGFR treatment."

P1 data • Preclinical • Oncology • Solid Tumor • YAP1

Src family kinase inhibition demonstrates antitumor activity in vitro and in patient-derived xenograft models of human cholangiocarcinoma (AACR 2024) - "NXP900 is a first-in-class, highly selective, SFK inhibitor with a novel mechanism of action which locks SFK in its closed and inhibited conformation, in contrast to other Src inhibitors such as dasatinib. NXP900 demonstrated therapeutic activity in vitro and in human PDX models. We are currently performing multi-omic approaches in NXP900 sensitive and resistant cell lines to unravel determinants of activity and resistance. Additional in vivo studies will be performed to determine effects of NXP900/GemCis and NXP900/anti-PDL-1 combination therapy."

Preclinical • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CCN1 • CTGF

First in human phase 1 trial of the SRC family kinase inhibitor NXP900 in patients with advanced solid tumors (AACR 2025) - P1 | "In its first-in-human clinical trial in patients with advanced solid tumors NXP900 was biologically active with an acceptable safety profile, supporting its continued clinical development."

Clinical • First-in-human • Metastases • P1 data • Oncology • Solid Tumor

Multiomic profiling identified biomarkers of response to selective Src family kinase inhibition in preclinical models of cholangiocarcinoma (AACR 2025) - "NXP900 is a highly selective SFK inhibitor a novel mechanism of action that locks SFKs in a closed, inhibited conformation, preventing interaction with substrate proteins, unlike other SFK inhibitors like dasatinib. This study identified molecular markers linked to response to SFK inhibition, which could be utilized for patient selection for NXP900 treatment. Further studies are validating these findings and exploring combination therapies to address resistance mechanisms."

Preclinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • EGFR • LYN • SYK

Overcoming osimertinib resistance in NSCLC with NXP900, a phase 1, highly selective and potent first-in-class total YES1/SRC inhibitor (AACR 2025) - "In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active "open" conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Despite high response rates to osimertinib in EGFR mutant lung cancer patients acquired resistance almost universally arises. Here we demonstrate that NXP900 in combination with osimertinib demonstrates potent synergy and prolonged inhibition of tumor growth in in vitro and in vivo NSCLC models of acquired osimertinib resistance. Altogether, these data suggest that NXP900 may have therapeutic potential in EGFR mutant cancers with acquired resistance to osimertinib."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

NXP900, a phase 1, first-in-class YES1/SRC inhibitor demonstrates potent single agent activity and synergy with ALK inhibitors in ALK resistant NSCLC models (AACR 2025) - "In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, lock SRC in the active "open" conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Despite high response rates to lorlatinib and long duration of response, acquired resistance almost universally arises. Here we demonstrate that NXP900 can potently inhibit cell proliferation of ALK resistant cell lines as a single agent and is synergistic with lorlatinib in NSCLC models harboring different variants of the ALK gene fusion. Altogether, these data suggest that NXP900 may have therapeutic potential in cancers with acquired resistance to ALK inhibitors."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4

Endocrine therapy-resistant luminal A breast cancer cell lines are sensitive to the novel YES1/SRC tyrosine kinase inhibitor, NXP900 (AACR 2025) - "Recent findings using ER+ cell lines show increased sensitivity with NXP900 as opposed to other kinase inhibitors, such as dasatinib or bosutinib. Additionally, our longitudinal data suggests that NXP900 is a strong therapeutic candidate to treat ER+ cell lines with acquired endocrine resistance. This study supports the potential translation of NXP900 into an adjuvant clinical setting, alongside endocrine therapies, to improve breast cancer treatment in patients with ER+ tumors."

Late-breaking abstract • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

NXP900, a novel YES1/SRC kinase inhibitor currently in clinical development, blocks YAP1 signaling in NSCLC cell lines (AACR 2025) - "Conversely, multi-kinase inhibitors dasatinib and bosutinib target the "open" conformation (type 1), thus promoting SFK association with signalling partners3. NXP900 prevents YAP1 nuclear localization and cell cycle progression in a panel of NSCLC cell lines, decreasing expression of total YAP1 and YES1. Our data suggests that NXP900, currently in a Phase1 dose escalation study, is an attractive and translatable combination partner that could synergize with existing targeted therapies against NSCLC when the Hippo pathway is dysregulated."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • YAP1

A phosphoproteomic LC-MS approach delineates Src-family kinase contributions to profibrotic signalling in lung fibroblasts (ERS LSC 2026) - "Here, we elaborate on a phosphoproteomic LC-MS approach to compare saracatinib and NXP900 and delineate specific contributions of the SFKs to TGF-?1-mediated profibrotic signalling. Kinase-substrate analyses comparing compounds highlighted phosphorylation of substrates downstream of AKT1/2/3, GSK3A/B, BRAF, MTOR, and PAK1/2 as differentially-regulated, while phosphorylation downstream of AURKA/B, MARK1/2, PIM1/2, and LATS1 showed agreement. Our data show differential regulation of TGF-?1-mediated SFK signalling by different mechanistic subclasses of SFK inhibition and further suggests that the SFKs may regulate TGF-?1-induced cytoskeletal organization independently of collagen synthesis."

Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • AKT1 • AURKA • BRAF • CDC42 • LATS1 • PIM1

A Phase 1b Clinical Study of NXP900 in Combination with Osimertinib in Patients with Advanced, EGFRMut+ Non-Small Cell Lung Cancer (Study NXP900-103) (Trial in Progress) (IASLC-TTLC 2026) - "The patient population, dose, dosing schedule and other operational characteristics for the expansion will be informed by data from the dose exploration phase. The primary objective of the dose exploration is to determine a safe and clinically active combination dose of NXP900 plus osimertinib."

Clinical • Combination therapy • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Nuvectis Pharma, Inc. Reports 2025 Financial Results and Business Highlights (The Manila Times) - "'...multiple potential data readouts in 2026. Our Phase 1b monotherapy study evaluating NXP900’s clinical potential in several molecularly and histologically-defined target tumors, and the combination study of NXP900 with osimertinib in patients with EGFR-mutated non-small cell lung cancer ('NSCLC') are enrolling patients. In addition, a combination with lorlatinib in ALK-positive NSCLC, is pending commencement.'...'We remain focused on operational execution and financial responsibility, and believe that our current cash position can take us through multiple potential NXP900 Phase 1b milestones and well into the second half of 2027.'"

P1 data • Trial status • Non Small Cell Lung Cancer

Multiomics-driven discovery of predictive biomarkers and strategies to overcome resistance to SFK-YAP inhibition in cholangiocarcinoma. (PubMed, bioRxiv) - "NXP900 also synergized with gemcitabine/cisplatin chemotherapy, enhancing antitumor efficacy in both in vitro and in vivo models. IL13RA-AKT signaling was upregulated in resistant models; NXP900 sensitivity could be restored with AKT or IL13RA2 inhibition. Together, these findings demonstrate the therapeutic potential of NXP900 as a novel YAP inhibitor in CCA and support further investigation in a clinical trial."

Biomarker • Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CD123 • IL13RA2

Study of NXP900 With Osimertinib in Subjects With Advanced, EGFR-Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Nuvectis Pharma, Inc.

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Yes/src kinase inhibitor nxp900, currently in clinical development, combines synergistically with fulvestrant against luminal a breast cancer cell lines in vitro and in vivo (SABCS 2025) - "Dose response studies were performed for NXP900, dasatinib and fulvestrant in a library of ER+ luminal A cell lines. Our results demonstrate that luminal A cancer cell lines are generally sensitive to NXP900 treatment and that in combination with endocrine therapy it is more synergistic than the standard-of-care combination of fulvestrant and CDK4/6 inhibitors. This study supports the potential translation of NXP900 into breast cancer patients alongside endocrine therapies to improve the treatment of ER+ tumors."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • FAT1 • HER-2 • YAP1

Nuvectis Pharma Announces the Initiation of the Phase 1b Study of NXP900 in Combination with Osimertinib in Patients with NSCLC (Nuvectis Pharma Press Release) - " Today marks the commencement of the first combination study of NXP900 as part of the Phase 1b program....'We expect 2026 to be an exciting year with multiple data readouts from both the single agent and combination studies, and we look forward to providing updates from the program throughout the year.'"

Trial status • Non Small Cell Lung Cancer

Characterisation of Src-family kinase inhibitors in lung fibroblasts shows distinct signalling complexes required for matrix synthesis and differentiation (BTS WM 2025) - "While less selective compounds showed inhibition of both processes, a novel, more selective and conformation-dependent inhibitor (NXP900) showed only inhibition of α-SMA expression, suggesting independent mechanisms for these processes. Cell-free kinome scan assays and cell-based phosphoproteomics revealed that more selective SFK inhibition does not affect TGF-β1-mediated mTOR signalling required for ECM synthesis, but does modulate cell signalling complexes associated with cytoskeletal organisation, focal adhesion, and cell-cell/substrate junctions. These results suggest specific roles for the SFKs in myofibroblast differentiation with implications for therapeutically targeting functional heterogeneity in pathological cell sub-populations in IPF."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • TGFB1

Nuvectis Pharma to Host a Virtual Key Opinion Leader Meeting to Discuss the NXP900 Phase 1b Program in Advanced Solid Tumors, Including the Combination with Osimertinib in NSCLC (GlobeNewswire) - "Event scheduled for Tuesday, December 2nd at 8:00 AM ET....The discussion will focus on key NXP900 preclinical and clinical data to date and the strategy for the monotherapy and combination components of the NXP900 Phase 1b clinical program."

Clinical data • Preclinical • Non Small Cell Lung Cancer