KRAS and RAS inhibitors

• ClinicalTrials.gov lists 322 ¹ interventional studies of KRAS or RAS inhibitors; 217 ² are active and 36 ³ are Phase 3.
• 226 ⁴ started between January 2023 and September 2026: 116 ⁵ with a US site and 91 ⁶ with a China site.
• Revolution Medicines' pan-RAS inhibitor daraxonrasib appears in 15 ⁷ new studies. KRAS G12D-directed programmes appear in 90 ⁸.
• Pancreatic cancer (79 ⁹ new studies) is catching up with non-small cell lung cancer (93 ¹⁰).

Trial starts went from 13 ¹¹ in 2020 to 37 ¹² in 2022 and 60 ¹³ in 2024, then 56 ¹⁴ in 2025. The plateau reflects a change of mix rather than a loss of interest: early G12C monotherapy studies are finishing while fewer, larger combination and first-line trials start.

The field is US-centred and industry-led. Studies with a US site went from 11 ¹⁵ in 2020 to 24 ¹⁶ in 2025. Studies with a China site rose from 1 ¹⁷ to 24 ¹⁸, as Chinese developers such as InventisBio, Genfleet with Innovent, Jacobio and Hengrui brought their own inhibitors into the clinic.

Among studies started since 2023, KRAS G12D-directed programmes lead with 90 ⁸. That group includes selective inhibitors (zoldonrasib, HRS-4642, INCB161734), a degrader (setidegrasib) and G12D-targeted vaccines and T-cell therapies.

The approved G12C drugs are now mostly in combination studies: sotorasib appears in 28 ²⁹ new studies and adagrasib in 25 ³⁰. Chinese G12C inhibitors, garsorasib, fulzerasib and glecirasib, appear in 31 ³¹. Next-generation G12C drugs designed for deeper target coverage include Lilly's olomorasib (14 ³²) and Roche's divarasib (8 ³³).

Revolution Medicines' daraxonrasib (15 ⁷) inhibits the active, GTP-bound form of RAS across mutations. Its Phase 3 programmes in pancreatic and lung cancer are the most-watched readouts in the category.

Non-small cell lung cancer is listed in 93 ¹⁰ studies started since 2023, and pancreatic cancer in 79 ⁹. Basket studies in advanced solid tumours account for 89 ³⁴ and colorectal cancer for 55 ³⁵.

Pancreatic cancer matters because the large majority of cases carry a KRAS mutation, most often G12D or G12V rather than G12C. Several first-line Phase 3 trials started in 2026 compare RAS inhibitors, alone or with chemotherapy, with gemcitabine and nab-paclitaxel. They include daraxonrasib, zoldonrasib, setidegrasib and INCB161734.

• Lumakras (sotorasib), approved 28 May 2021 (NDA 214665)
• Krazati (adagrasib), 12 December 2022 (NDA 216340)

China's regulator has also approved domestic G12C inhibitors in previously treated lung cancer: fulzerasib in August 2024 (GenFleet) and garsorasib in November 2024 (InventisBio). G12C drugs gave only modest benefit as single agents in lung cancer, which is why the field moved to combinations and to broader RAS coverage.

• Another G12C inhibitor is hard to justify. At least seven are in the clinic and two are approved in the US. New value is in G12D, G12V and pan-RAS chemistry and in degraders.
• Resistance biology is the opening. Adaptive resistance through upstream receptor signalling and secondary RAS mutations limits every inhibitor so far. Rational combinations, such as SHP2, SOS1, EGFR or immunotherapy partners, and drugs that hit the active RAS state are where smaller teams can differentiate.
• Pancreatic cancer changes the economics. It is hard to treat and has few options, so a real survival benefit would be both commercially large and fast to approve. It also means fragile patients and trials that fail often.
• Expect big-company competition and deal flow. 116 ⁵ of the studies started since 2023 have a US site and most are industry-sponsored. Licensing Chinese G12D and pan-RAS chemistry is an active deal area.

Every trial count is the totalCount of one ClinicalTrials.gov API v2 query, retrieved on 26 September 2026. Each numbered citation opens a record whose source link re-runs the query. The track includes interventional studies whose record names a KRAS or RAS inhibitor by drug name, development code or class phrase.

The G12D bar matches intervention names containing "G12D" and so includes vaccines and cell therapies, not only small molecules. Site-country counts overlap and China-only registrations are missing. Approval dates come from Drugs@FDA.