Breakthrough Clinical Results
Nuvectis Pharma, Inc. announced upcoming poster presentations for NXP900 at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. NXP900, an oral small molecule inhibitor of the SRC Family of Kinases (SFK), including SRC and YES1, is currently being evaluated in a Phase 1b program. The presentations will cover clinical safety, pharmacokinetics, pharmacodynamics, cytochrome P450 interactions, and tumor growth inhibition in FAT1 mutated xenograft models.
Key Highlights
- Nuvectis Pharma to present NXP900 data at the AACR-NCI-EORTC conference.
- Presentations will cover clinical safety and pharmacokinetics of NXP900.
- NXP900 inhibits tumor growth in FAT1 mutated xenograft models.
- NXP900 is an oral small molecule inhibitor of SRC and YES1 kinases.
Incidence and Prevalence
Latest Global Cancer Estimates
Global Burden
Recent data indicates that in 2022, rare cancers accounted for 26.7% of all new cancer cases (5,347,784 cases) and 30% of all cancer-related deaths (2,959,369 deaths) worldwide. Current global evidence projects a 47% rise in cancer cases for the period 2020-2040.
Regional Patterns
Europe recorded 4,471,422 new cancer cases in 2022 with an age-standardized incidence rate (ASR) of 280 per 100,000 and a cumulative risk of 27.9% by age 75. Males accounted for 2,359,303 cases (ASR 319.6), while females had 2,112,119 cases (ASR 253.4).
Northern and Western Europe had the highest incidence rates, with Denmark leading at 374.7 per 100,000. Eastern Europe had the highest mortality, with 1,091,871 deaths (ASR 135.3), reflecting late diagnoses and limited access to treatment.
South and South-East Asia reported 177,258 incident cases and 98,735 deaths from oral cancer in 2022, accounting for 52% of total global deaths from oral cancer.
Cancer Types
Bladder cancer was the most common rare cancer globally in 2022, with an incidence rate of 5.58 per 100,000, followed by non-Hodgkin lymphoma (5.57) and leukemia (5.26). Mortality rates were highest for pancreatic, esophageal, and brain cancers.
The age-standardized rates (ASRs) of central nervous system (CNS) cancer incidence and mortality were 3.5 and 2.8 per 100,000 globally, with Southern Europe (ASR = 6.0) and Western Asia (ASR = 4.2) having the highest incidence and mortality, respectively.
In Europe, prostate and breast cancers were the most common in males and females, respectively. Lung cancer had a lower incidence (ASR 24.7) but the highest mortality (ASR 17.7), while pancreatic cancer showed high fatality (ASR 6.3, mortality ASR 5.6).
Geographical Disparities
Significant regional disparities were observed, with Europe and North America reporting the highest incidence rates for bladder cancer and leukemia, while Asia bore the largest absolute burden of rare cancers.
Cancer incidence varies markedly across GRELL countries (Group for Cancer Epidemiology and Registration in Latin Language Countries) and within several countries. The area with the highest male incidence had an ASR 4.3 times higher than the area with the lowest incidence, while for females, this ratio was 3.3.
Survival Rates
In Zhejiang Province, China, during 2018-2019, the age-standardized 5-year relative survival (RS) and net survival (NS) for overall cancer was 47.5% and 48.6%, respectively. The age-standardized 5-year RS for cancers of women (55.4%) was higher than that of men (40.0%).
In Southeast Asia, breast cancer survival rates were 88.8% at 1 year, 73.8% at 3 years, 70.8% at 5 years, and 49.3% at 10 years.
Key Unmet Needs and Targeted Populations in Cancer Treatment
Major Treatment Challenges
Metastatic disease remains the main cause of cancer mortality, requiring therapies focused on prevention of metastatic disease by targeting metastasis causes (hypoxia, metabolism changes, tumor microenvironment) and metastasis roots (angiogenesis, epithelial-mesenchymal transition, migration, invasion).
Immunotherapy limitations persist due to individual differences between patients, making clinical application limited. There's a critical need for specific biomarkers to avoid damage in healthy tissues and treatment resistance. Immunotherapy requires customization for different cancer types due to variations in targets.
Multimodal treatment approaches need optimization, particularly combining radiotherapy with immunomodulating agents and adding hyperthermia (HT) to boost anti-tumor immune responses.
Targeted Populations
Several specific patient populations are being targeted in clinical trials:
- Patients with metastatic hormone-sensitive prostate cancer (HSPC) for combination therapies with ADT plus docetaxel, abiraterone acetate/prednisone, apalutamide, enzalutamide, or darolutamide
- Rectal cancer patients with good response after neoadjuvant chemoradiotherapy
- Patients with stage I clear cell and serous uterine carcinoma for different adjuvant approaches
- NSCLC patients with MET exon14 skipping mutations for MET-targeted tyrosine kinase inhibitors
- Patients with HER-2 positive breast cancer for monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors
Disparities and Underrepresented Groups
Women are underrepresented in clinical trials leading to FDA oncology drug approvals (39.7% female participants vs. 44.6% incidence). Gender representation varies by tumor type, with women underrepresented in thyroid cancer trials.
Black patients with colorectal cancer face significant survival disparities compared to White patients, with this disparity increasing over the past 20 years.
Emerging Approaches
Novel approaches being explored include: * Targeting acidic microenvironment using pH (Low) Insertion Peptide (pHLIP) * Biomimetic nanodelivery systems (BNDS) for targeted drug delivery * Protozoa and their components showing anti-tumor potential * Natural products like mushroom extracts showing potential anticancer activity * Microorganism-based approaches for diagnosis and treatment
Neglected Areas
Rare cancers (less than 15 cases per 100,000 annually) have limited survivorship research, creating barriers to identifying needs and developing interventions. Few survivorship grants focus on cancers like multiple myeloma, testicular cancer, rectal cancer, thyroid cancer, and cervical cancer.
Primary central nervous system lymphoma (PCNSL) patients face poor outcomes and limited treatment options, especially for elderly patients or those with relapsed/refractory disease.
Drugs Being Trialled for the Same Indication as NXP900
Dasatinib
Dasatinib is being investigated for the same indication as NXP900, which is Low grade serous ovarian carcinoma (LGSOC). Both drugs target the SRC family kinases (SFKs), though with different mechanisms:
- NXP900 locks SRC in the "closed" conformation, inhibiting both kinase-dependent catalytic activity and kinase-independent functions
- Dasatinib binds to SRC in the active "open" conformation, which allows SRC and other SFKs to act as a scaffold to promote tumorigenesis through non-catalytic functions
Intervention Model for Dasatinib
The intervention model for dasatinib includes combination therapy with trametinib (a MEK inhibitor). This combination was selected based on demonstrated favorable synergy across multiple LGSOC models, with a maximum zero interaction potency synergy score of 46.9. Research suggests that SFK inhibition is the likely driver of synergy between dasatinib and trametinib.
The development process for this intervention model included: - Initial high throughput drug screening of 1610 agents across a panel of 6 LGSOC cell lines (3 RAS/RAF-mutant, 3 RAS/RAF-wildtype) - Identification of 16 hits prioritized based on >50% reduction in nuclei counts in over half of screened cell lines at 1000 nM concentration - Validation through dose-response analysis across 9 LGSOC models and 5 high grade serous comparator lines - Final selection of 11 compounds that passed validation, with dasatinib being one of the four agents of greatest interest
Bosutinib
Bosutinib is also mentioned as a multi-targeted kinase inhibitor that inhibits SRC in the "open" conformation similar to dasatinib. While it shares a mechanism with dasatinib, the context does not provide specific details about its current trial status for LGSOC or its intervention model.
NXP900's Unique Properties
It's worth noting that while these drugs target the same family of kinases, NXP900 exhibits a unique target selectivity profile with sub-nanomolar activity against SFK members over other kinases. NXP900 is currently being dosed in a phase 1 clinical trial and has demonstrated a similar trametinib synergy profile to dasatinib in LGSOC models.
Additionally, esophageal squamous cell carcinomas and head and neck squamous cell carcinomas were found to be highly sensitive to NXP900 treatment in cell culture and in vivo.