ROS1 Inhibitors
11 drugsAbout ROS1
ROS1, or ROS Proto-Oncogene 1, is a receptor tyrosine kinase. It functions in cell growth and differentiation. Aberrant ROS1 activity is implicated in various cancers.
Human genetics provide moderate support for ROS1 as a therapeutic target (max score 0.59). Genetic associations include short stature (0.59), male infertility (0.55), and hemorrhoid (0.53), with loss-of-function variants increasing risk. Activation of ROS1 is likely beneficial.
Eleven FDA-approved small molecule drugs target ROS1, including CABOMETYX, XALKORI and ROZLYTREK. Seven drugs are approved for oncology indications, while four target other therapeutic areas. The first drug was approved in 2011, and the most recent in 2025.
ROS1 Genetic Evidence Moderate
Genetic evidence offers moderate support for ROS1, with a maximum score of 0.59.
Further research into the genetic associations may reveal novel therapeutic opportunities beyond oncology.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in phenotype, reproductive system or breast disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
9 totalGWAS and other genetic studies link ROS1 to 9 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 4 strong
max H4: 0.93eQTL/pQTL signals for ROS1 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top ROS1 Drugs
Eleven companies have approved drugs targeting ROS1, including Roche, Takeda and Novartis.
The presence of many players suggests a competitive market, requiring a differentiated strategy for new entrants.
ROS1 Drug Modality Landscape
Modalities
Routes of Administration
ROS1 is amenable to small molecule drugs, with oral options available for convenient dosing.
Explore alternative modalities like antibodies or PROTACs to differentiate from existing therapies.
ROS1 Clinical Trials 454 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on ROS1. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 150 | 78 | 25 | 47 | 76% |
| Phase 2 | 234 | 77 | 43 | 111 | 64% |
| Phase 3 | 54 | 14 | 4 | 36 | 78% |
| Phase 4 | 16 | 3 | 2 | 11 | 60% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
7 Phase 3 trials testing approved ROS1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting ROS1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
ROS1 Drug Approval Timeline (2011 - 2025)
The approval timeline for ROS1 inhibitors spans 15 years, from 2011 to 2025.
The continued approval of new drugs indicates ongoing interest, but also suggests potential market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 10 companies competing
- • Market share by company
Full Drug Portfolio
- • All 11 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 11-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 176 (34 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on ROS1. A trial counts if an approved drug acting on ROS1 is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.