KRAS Inhibitors for Cancer Treatment
Daromakrasib (RMC-6236) demonstrated a significant overall survival benefit in a Phase 3 trial for metastatic pancreatic cancer on April 20, 2026, nearly doubling median OS compared to standard chemotherapy and reducing the risk of death by 60%. As of April 20, 2026: Daromakrasib has shown positive Phase 3 results, while the FDA granted Fast Track Designation to Verastem Oncology's VS-7375, and the clinical trial for MRTX1133 was terminated due to formulation issues. Incyte's INCB161734, which also showed antitumor activity in KRAS G12D-mutated PDAC, is planning a global Phase III trial despite a temporary clinical hold due to a Grade 5 pneumonitis case. Revolution Medicines announced a median overall survival of 13.2 months for daraxonrasib, and researchers continue to explore new pan-KRAS inhibitors like BI-2865, BI-2493, ETX-929, and Adlai Nortye's new inhibitors. Setidegrasib, a KRAS degrader, has also shown encouraging responses in lung and pancreatic cancer patients in Phase 1 trials.
Timeline
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April 2026 — 5 developments
Daromakrasib (RMC-6236) has demonstrated a significant overall survival benefit in a Phase 3 trial f…
Daromakrasib (RMC-6236) has demonstrated a significant overall survival benefit in a Phase 3 trial for metastatic pancreatic cancer, nearly doubling median OS compared to standard chemotherapy and reducing the risk of death by 60%. Additionally, INCB161734 has shown antitumor activity in KRAS G12D-mutated PDAC, prompting the planning of a global Phase III trial.
The FDA has granted Fast Track Designation to Verastem Oncology's oral KRAS G12D inhibitor, VS-7375, for pancreatic cancer.
The FDA has granted Fast Track Designation to Verastem Oncology's oral KRAS G12D inhibitor, VS-7375, for pancreatic cancer. Separately, the clinical trial for MRTX1133, another KRAS G12D inhibitor, was terminated due to formulation and pharmacokinetic issues. Research continues with Ensem Therapeutics' ETX-929 and Adlai Nortye's new inhibitors.
Revolution Medicines announced positive topline Phase III results for daraxonrasib (RMC-6236) in metastatic pancreatic cancer, demonstrating a median overall survival of 13.
Revolution Medicines announced positive topline Phase III results for daraxonrasib (RMC-6236) in metastatic pancreatic cancer, demonstrating a median overall survival of 13.2 months, nearly doubling that of standard chemotherapy. Incyte's INCB161734 is on a temporary clinical hold due to a Grade 5 pneumonitis case.
New pan-KRAS inhibitors BI-2865 and BI-2493 are demonstrating potent and reversible inhibition, while a uniquely engineered RNA drug targeting KRAS G12V is in preclinical studies.
New pan-KRAS inhibitors BI-2865 and BI-2493 are demonstrating potent and reversible inhibition, while a uniquely engineered RNA drug targeting KRAS G12V is in preclinical studies.
Phase 1 clinical trial results for setidegrasib, a KRAS degrader targeting the G12D mutation, have b…
Phase 1 clinical trial results for setidegrasib, a KRAS degrader targeting the G12D mutation, have been published, showing encouraging responses in lung and pancreatic cancer patients. Researchers are also exploring new pan-KRAS inhibitors, and Penn Medicine plans to investigate pan-RAS inhibitors for precancerous pancreatic lesions.
March 2026 — 10 developments
Revolution Medicines will present new Phase 1 data for zoldonrasib (RMC-9805), a selective inhibitor…
Revolution Medicines will present new Phase 1 data for zoldonrasib (RMC-9805), a selective inhibitor for KRAS G12D mutant non-small cell lung cancer, at the AACR Annual Meeting in April 2026. Findings from Phase 1/2 studies on daraxonrasib (RMC-6236), a multi-selective inhibitor for metastatic pancreatic ductal adenocarcinoma, will also be featured, alongside preclinical research on new RAS(ON) inhibitors.
INCB161734, a KRAS G12D inhibitor, has shown promising results in advanced pancreatic cancer patient…
INCB161734, a KRAS G12D inhibitor, has shown promising results in advanced pancreatic cancer patients, with some experiencing disease control and objective responses, though a clinical hold was noted due to pneumonitis. BlossomHill Therapeutics and D3 Bio are developing next-generation pan-KRAS inhibitors targeting various mutations, showing potent inhibition in preclinical studies.
Bristol Myers Squibb has discontinued the development of MRTX1133, a selective oral KRAS G12D inhibitor, despite no safety concerns being identified.
Bristol Myers Squibb has discontinued the development of MRTX1133, a selective oral KRAS G12D inhibitor, despite no safety concerns being identified. The decision was reportedly influenced by pharmacokinetic factors. This marks a significant shift in the clinical progression of this investigational cancer therapy.
MRTX1133, a selective KRAS G12D inhibitor, has demonstrated potent preclinical antitumor efficacy, particularly in pancreatic ductal adenocarcinoma.
MRTX1133, a selective KRAS G12D inhibitor, has demonstrated potent preclinical antitumor efficacy, particularly in pancreatic ductal adenocarcinoma. Research is focused on combining MRTX1133 with chemotherapy to reduce tumor growth and overcome resistance, with a phase I/II clinical trial underway.
Revolution Medicines' investigational pan-RAS inhibitor, Daraxonrasib (RMC-6236), has demonstrated e…
Revolution Medicines' investigational pan-RAS inhibitor, Daraxonrasib (RMC-6236), has demonstrated early activity and a manageable safety profile in patients with RAS-mutant pancreatic adenocarcinoma. The drug has received FDA breakthrough therapy designation for previously treated metastatic PDAC with KRAS G12X mutations, and a Phase 3 trial is underway.
Verastem Oncology's investigational oral KRAS G12D inhibitor VS-7375 demonstrated a promising early …
Verastem Oncology's investigational oral KRAS G12D inhibitor VS-7375 demonstrated a promising early safety profile and preliminary antitumor activity in patients with advanced solid tumors harboring a KRAS G12D mutation. In the Phase 1/2a VS-7375-101 trial, no dose-limiting toxicities were observed at daily doses of 400 mg and 600 mg, and 80% of efficacy-evaluable patients experienced tumor reduction. The FDA granted VS-7375 Fast Track Designation in July 2025 for KRAS G12D-mutated pancreatic cancer.
Verastem Oncology has outlined a new development pathway for its KRAS G12D inhibitor, VS-7375, for p…
Verastem Oncology has outlined a new development pathway for its KRAS G12D inhibitor, VS-7375, for pancreatic, colorectal, and non-small cell lung cancer, following discussions with the US Food and Drug Administration. The investigational oral inhibitor has demonstrated a promising early safety profile and preliminary antitumor activity in pretreated patients with advanced solid tumors harboring a KRAS G12D mutation.
Incyte's KRAS G12D inhibitor, INCB161734, has been placed on clinical hold in four European countries following a Grade 5 pneumonitis death in a participant.
Incyte's KRAS G12D inhibitor, INCB161734, has been placed on clinical hold in four European countries following a Grade 5 pneumonitis death in a participant. Three additional cases of pneumonitis were also reported, all associated with the 1.2g dose.
The KRAS G12D inhibitor INCB161734 demonstrated disease control in nearly 80% of heavily pretreated advanced pancreatic cancer patients, with 37% achieving objective responses.
The KRAS G12D inhibitor INCB161734 demonstrated disease control in nearly 80% of heavily pretreated advanced pancreatic cancer patients, with 37% achieving objective responses. Verastem Oncology's inhibitor VS-7375 has cleared multiple dose levels in early studies without dose-limiting toxicities, allowing for continued dose escalation. Additionally, Erasca and Tango Therapeutics are collaborating to evaluate a combination therapy for RAS-mutant cancers.
A PNAS study published on December 2, 2025, details a triple combination therapy involving daraxonra…
A PNAS study published on December 2, 2025, details a triple combination therapy involving daraxonrasib that induced complete regression of pancreatic cancer tumors in mice with no evidence of resistance. Verastem Oncology reported on March 4, 2026, that their oral KRAS G12D inhibitor VS-7375 cleared multiple dose levels in early studies without dose-limiting toxicities, allowing dose escalation to continue.
February 2026 — 4 developments
Erasca presented updates on its pan-RAS inhibitor ERAS-0015 and pan-KRAS inhibitor ERAS-4001, with ERAS-0015 showing a potency advantage over RMC-6236.
Erasca presented updates on its pan-RAS inhibitor ERAS-0015 and pan-KRAS inhibitor ERAS-4001, with ERAS-0015 showing a potency advantage over RMC-6236. Separately, a PNAS study details a triple combination therapy including daraxonrasib that induced complete regression of pancreatic cancer tumors in mice with no evidence of resistance.
Preliminary Phase 1 data for INCB161734 presented at ASCO GI 2026 showed a disease control rate of 7…
Preliminary Phase 1 data for INCB161734 presented at ASCO GI 2026 showed a disease control rate of 73% at 600 mg once daily and 86% at 1200 mg once daily in patients with advanced pancreatic cancer. New research also suggests combining chemotherapy with KRAS inhibitors may enhance treatment effectiveness, and that resistance to KRAS G12D inhibitors can be overcome by BET inhibition.
Incyte has announced that based on positive clinical data from a Phase 1 trial of INCB161734 in pati…
Incyte has announced that based on positive clinical data from a Phase 1 trial of INCB161734 in patients with advanced pancreatic ductal adenocarcinoma, a Phase 3 study is expected to commence in the first quarter of 2026. This marks a significant step forward in the development of this KRAS G12D inhibitor.
Verastem Oncology is advancing its clinical development program for VS-7375, a selective oral KRAS G…
Verastem Oncology is advancing its clinical development program for VS-7375, a selective oral KRAS G12D inhibitor, and expects to report an interim update on its Phase 1/2 trial in the first half of 2026. Early data for INCB161734 show a manageable safety profile and evidence of antitumor activity in heavily pretreated patients with KRAS G12D-mutated PDAC. Additionally, the investigational oral KRAS G12D inhibitor VS-7375 has demonstrated a promising early safety profile and preliminary antitumor activity in pretreated patients with advanced solid tumors harboring a KRAS G12D mutation.
January 2026 — 9 developments
Revolution Medicines has expanded its KRAS inhibitor research with a new molecule, RMC-5127, targeting KRAS G12V, which has just entered its first-in-human trial.
Revolution Medicines has expanded its KRAS inhibitor research with a new molecule, RMC-5127, targeting KRAS G12V, which has just entered its first-in-human trial.
Verastem Oncology discontinued its RAMP 203 Phase 1/2 trial for KRAS G12C-mutated non-small cell lun…
Verastem Oncology discontinued its RAMP 203 Phase 1/2 trial for KRAS G12C-mutated non-small cell lung cancer to prioritize resources for the clinical development of the oral KRAS G12D inhibitor VS-7375.
A new study reported that a triple-targeted drug combination, including the KRAS inhibitor daraxonra…
A new study reported that a triple-targeted drug combination, including the KRAS inhibitor daraxonrasib, achieved complete and lasting regression of pancreatic tumors in preclinical models, demonstrating potential to overcome treatment resistance.
Research indicates that resistance to the KRAS G12D inhibitor MRTX1133 is associated with increased …
Research indicates that resistance to the KRAS G12D inhibitor MRTX1133 is associated with increased sensitivity to BET inhibition, with murine models showing that BET inhibition cooperated with MRTX1133 to significantly extend overall survival.
Preliminary Phase 1 results for Incyte's oral KRAS G12D inhibitor INCB161734 showed promising early …
Preliminary Phase 1 results for Incyte's oral KRAS G12D inhibitor INCB161734 showed promising early clinical efficacy and molecular response in advanced pancreatic cancer patients, with common side effects being nausea and diarrhea. Revolution Medicines' daraxonrasib (RMC-6236) received Orphan Drug Designation from the FDA for pancreatic cancer treatment, building on promising safety and efficacy data from its Phase 1/1b trial.
Preliminary Phase 1 results for INCB161734, an oral KRAS G12D inhibitor, show a manageable safety pr…
Preliminary Phase 1 results for INCB161734, an oral KRAS G12D inhibitor, show a manageable safety profile with mostly grade 1/2 adverse events in patients with advanced pancreatic ductal adenocarcinoma. Updated data from a Phase 1 study presented at ASCO GI indicated a 78% disease control rate and a 37% objective response rate among evaluable patients. Additionally, VS-7375 has received Fast Track Designation from the FDA for KRAS G12D-mutated advanced pancreatic cancer.
Daraxonrasib received FDA breakthrough therapy designation for treating metastatic pancreatic cancer with KRAS G12X mutations.
Daraxonrasib received FDA breakthrough therapy designation for treating metastatic pancreatic cancer with KRAS G12X mutations. Separately, preliminary clinical data for INCB161734 showed nearly 80% disease control in heavily pretreated advanced pancreatic cancer patients.
Incyte's oral KRAS G12D inhibitor, INCB161734, has shown a manageable safety profile and promising e…
Incyte's oral KRAS G12D inhibitor, INCB161734, has shown a manageable safety profile and promising early efficacy in patients with advanced solid tumors, including KRAS G12D-mutated pancreatic ductal adenocarcinoma. A Phase 1 study reported a disease control rate of 78% for the investigational drug.
Early clinical data for INCB161734, a novel oral KRAS G12D inhibitor, presented at ASCO GI 2026, sho…
Early clinical data for INCB161734, a novel oral KRAS G12D inhibitor, presented at ASCO GI 2026, shows a manageable safety profile as monotherapy and in combination with chemotherapy for patients with advanced pancreatic ductal adenocarcinoma.
November 2025 — 1 developments
MRTX1133, a KRAS G12D inhibitor, has advanced to Phase 1 clinical trials, showing tumor shrinkage in four out of five patients with advanced KRAS G12D-mutant cancers.
MRTX1133, a KRAS G12D inhibitor, has advanced to Phase 1 clinical trials, showing tumor shrinkage in four out of five patients with advanced KRAS G12D-mutant cancers. Revolution Medicines reported that its KRAS G12D-selective inhibitor, zoldonrasib (RMC-9805), has demonstrated encouraging safety and antitumor activity in patients with previously treated non-small cell lung cancer.
October 2025 — 3 developments
A comprehensive review of KRAS drug development in pancreatic cancer highlighted the shift towards G…
A comprehensive review of KRAS drug development in pancreatic cancer highlighted the shift towards G12D inhibitors like MRTX1133 and pan-RAS inhibitors like daraxonrasib, with numerous agents in clinical trials.
Verastem's KRAS G12D inhibitor VS-7375 demonstrated a 41% overall response rate in a clinical trial with heavily pre-treated pancreatic cancer patients, with 91.
Verastem's KRAS G12D inhibitor VS-7375 demonstrated a 41% overall response rate in a clinical trial with heavily pre-treated pancreatic cancer patients, with 91.5% experiencing disease control. Separately, a new study suggests resistance to MRTX1133 is associated with increased sensitivity to BET inhibition, with combination therapy showing extended survival in murine models.
Incyte presented preliminary Phase 1 data for its KRAS G12D inhibitor, INCB161734, in advanced pancreatic ductal adenocarcinoma, with a data cut-off of August 1, 2025.
Incyte presented preliminary Phase 1 data for its KRAS G12D inhibitor, INCB161734, in advanced pancreatic ductal adenocarcinoma, with a data cut-off of August 1, 2025. The data showed evidence of clinical benefit in 83 patients and a manageable safety profile with mostly Grade 1 gastrointestinal toxicities. The trial is ongoing, with results expected in 2026.
August 2025 — 1 developments
A review article emphasized the critical role of KRAS in pancreatic cancer and noted that the recent…
A review article emphasized the critical role of KRAS in pancreatic cancer and noted that the recent approval of KRAS inhibitors for other cancers has shattered the "undruggable" perception, fueling hope for breakthroughs in PDAC therapy.
July 2025 — 3 developments
Revolution Medicines announced topline results from the Phase 3 RASolute 302 trial for daraxonrasib (RMC-6236) in patients with metastatic pancreatic ductal adenocarcinoma.
Revolution Medicines announced topline results from the Phase 3 RASolute 302 trial for daraxonrasib (RMC-6236) in patients with metastatic pancreatic ductal adenocarcinoma. The trial demonstrated statistically significant improvements in overall survival and progression-free survival compared to standard-of-care chemotherapy. The company plans to submit these data to regulatory authorities and present them at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Verastem Oncology's oral KRAS G12D inhibitor, VS-7375, received FDA Fast Track designation for local…
Verastem Oncology's oral KRAS G12D inhibitor, VS-7375, received FDA Fast Track designation for locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) with KRAS G12D mutation, for both first-line treatment and after prior systemic therapy.
MRTX1133, a reversible KRAS G12D inhibitor, was discontinued from Phase 1 trials in March 2025 due to formulation challenges and suboptimal pharmacokinetics.
MRTX1133, a reversible KRAS G12D inhibitor, was discontinued from Phase 1 trials in March 2025 due to formulation challenges and suboptimal pharmacokinetics. Additionally, Daraxonrasib (RMC-6236), a pan-RAS(ON) inhibitor, is showing encouraging early clinical results for RAS-driven cancers and is undergoing a large international Phase 3 trial.
May 2025 — 1 developments
Initial safety and efficacy findings for VS-7375 in advanced solid tumors, including PDAC, were pres…
Initial safety and efficacy findings for VS-7375 in advanced solid tumors, including PDAC, were presented at the ASCO Annual Meeting, showing a 52% overall response rate and 100% disease control rate in PDAC patients with KRAS G12D mutation.
April 2025 — 1 developments
The FDA approved an investigational new drug (IND) application for VS-7375, an oral KRAS G12D inhibi…
The FDA approved an investigational new drug (IND) application for VS-7375, an oral KRAS G12D inhibitor, for the treatment of patients with advanced solid tumors, including pancreatic cancer.
August 2024 — 1 developments
Further research highlighted that chemotherapy could enhance the effectiveness of KRAS inhibitors in…
Further research highlighted that chemotherapy could enhance the effectiveness of KRAS inhibitors in pancreatic cancer by shutting down different cellular instructions that drive cancer cell growth, potentially preventing resistance.
July 2024 — 1 developments
Memorial Sloan Kettering Cancer Center researchers published findings on a new mechanism of resistan…
Memorial Sloan Kettering Cancer Center researchers published findings on a new mechanism of resistance to KRAS inhibitors in pancreatic cancer models, identifying opportunities to improve treatment effectiveness, particularly for the aggressive 'basal' subtype.
June 2024 — 1 developments
Studies published in Cancer Discovery demonstrated that combining chemotherapy with experimental KRA…
Studies published in Cancer Discovery demonstrated that combining chemotherapy with experimental KRAS inhibitors, such as MRTX1133, significantly reduced tumor growth and spread in mouse models of pancreatic cancer, suggesting a strategy to overcome resistance.
October 2023 — 1 developments
Revolution Medicines presented promising anti-tumor and safety data for its RAS inhibitor RMC-6236 i…
Revolution Medicines presented promising anti-tumor and safety data for its RAS inhibitor RMC-6236 in patients with previously treated non-small cell lung cancer and pancreatic ductal adenocarcinoma. In 40 efficacy-evaluable NSCLC patients, the objective response rate was 38% and the disease control rate was 85%. For pancreatic ductal adenocarcinoma patients, median progression-free survival was 8.5 months and median overall survival was 14.5 months.
January 2023 — 2 developments
Mirati Therapeutics announced that the U.
Mirati Therapeutics announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for MRTX1133, a potential first-in-class oral KRASG12D selective inhibitor. This clearance allows for the initiation of Phase 1 clinical evaluation of MRTX1133, which targets KRASG12D mutations found in approximately 180,000 patients in the US and Europe, for whom there are currently no targeted treatment options.
Despite the success of G12C inhibitors in lung cancer, it became clear that these drugs had limited …
Despite the success of G12C inhibitors in lung cancer, it became clear that these drugs had limited applicability in pancreatic cancer, where the G12C mutation is rare (1-2% of cases), shifting research focus to other prevalent mutations like G12D.
December 2022 — 1 developments
Adagrasib (Krazati), another KRAS G12C inhibitor, received accelerated FDA approval for NSCLC, further expanding treatment options for this specific KRAS mutation.
Adagrasib (Krazati), another KRAS G12C inhibitor, received accelerated FDA approval for NSCLC, further expanding treatment options for this specific KRAS mutation.
May 2021 — 1 developments
Sotorasib (Lumakras), the first KRAS G12C inhibitor, received accelerated FDA approval for treating …
Sotorasib (Lumakras), the first KRAS G12C inhibitor, received accelerated FDA approval for treating non-small cell lung cancer (NSCLC), validating the concept of directly targeting KRAS mutations.
January 2013 — 1 developments
After decades of KRAS being considered "undruggable," a pivotal discovery was made regarding a crypt…
After decades of KRAS being considered "undruggable," a pivotal discovery was made regarding a cryptic allosteric site in KRAS G12C, opening the door for the development of direct KRAS inhibitors.