Revolution Medicines Announces U.S. FDA Breakthrough Therapy Designation for RASONQUE™ (daraxonrasib) in Combination with Chemotherapy for First Line Metastatic Pancreatic Cancer

FDA breakthrough status could accelerate development of RASONQUE plus chemotherapy for newly diagnosed metastatic pancreatic cancer patients in the U.S.

Rhea-AI Summary

Revolution Medicines (RVMD) received U.S. FDA Breakthrough Therapy Designation for RASONQUE (daraxonrasib) with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic adenocarcinoma (PDAC).

The designation covers treatment-naïve metastatic PDAC in combination with this multiagent chemotherapy regimen and is based on preliminary Phase 1/2 RMC-GI-102 data in RAS mutant metastatic PDAC, where the regimen showed encouraging antitumor activity and a manageable safety profile. These results informed RASolute 303, an ongoing global Phase 3 trial evaluating RASONQUE as monotherapy and with chemotherapy versus chemotherapy alone in previously untreated metastatic PDAC, regardless of tumor RAS genotype. RASONQUE already has U.S. approval as an oral therapy for adults with metastatic PDAC after at least one prior systemic therapy or who are not candidates for multiagent systemic therapy, while first-line combination use remains investigational.

Positive

• Breakthrough Therapy Designation granted for RASONQUE + GnP in first-line metastatic PDAC
• Third Breakthrough Therapy Designation for RASONQUE and fifth across company’s RAS(ON) portfolio
• RASONQUE already FDA approved for metastatic PDAC after ≥1 prior therapy or for patients not candidates for multiagent systemic therapy
• Phase 1/2 RMC-GI-102 data showed encouraging antitumor activity and manageable safety for RASONQUE + GnP in treatment-naïve RAS mutant metastatic PDAC
• Global Phase 3 RASolute 303 ongoing in previously untreated metastatic PDAC, evaluating RASONQUE monotherapy and combination versus GnP alone

Negative

• Dermatologic toxicity in PDAC trials occurred in 86% of RASONQUE-treated patients, with 10% Grade 3
• Stomatitis occurred in 57% of patients, 9% Grade 3; diarrhea in 63%, 6% Grade 3
• Gastrointestinal perforation occurred in 0.9% of patients, including one Grade 4 event and one fatal event
• Interstitial lung disease/pneumonitis occurred in 2.4% of patients, with 0.9% Grade 3 and one fatal event
• Serious adverse reactions occurred in 30% of patients; adverse reactions led to permanent discontinuation in 2.9%
• RASONQUE carries an embryo-fetal toxicity warning and requires contraception for patients and partners during treatment and 1 week after last dose

News Explained

The designation places RASONQUE’s first-line chemotherapy combination in an FDA program intended to expedite development and review, but it does not authorize that use: the combination remains investigational, with safety and efficacy not yet established.

Market Context

0.21% was RVMD's pre-publication move; the designation extended RASONQUE's development into treatmen...

Analysis

0.21% was RVMD's pre-publication move; the designation extended RASONQUE's development into treatment-naïve PDAC, following a 1.92% 24-hour reaction around the Aug 26 FDA approval event.

Key Figures

Breakthrough Therapy Designations: 3rd for RASONQUE; 5th across the portfolio Trial Phase: Phase 1/2 Dermatologic Toxicity: 86%; 10% Grade 3 +2 more

Breakthrough Therapy Designations

3rd for RASONQUE; 5th across the portfolio

Revolution Medicines RAS(ON) inhibitors

Trial Phase

Phase 1/2

RMC-GI-102 trial supporting the designation

Dermatologic Toxicity

86%; 10% Grade 3

Clinical trials in pancreatic adenocarcinoma

Stomatitis

57%; 9% Grade 3

Clinical trials in pancreatic adenocarcinoma

Diarrhea

63%; 6% Grade 3

Clinical trials in pancreatic adenocarcinoma

Historical Context

2 past events · Latest: Aug 26

2 events

1. Aug 26

   FDA approval

   24h Move

   +1.9%

   FDA approved RASONQUE for previously treated metastatic PDAC after Phase 3 survival and progression-free survival results.

2. Aug 5

   Earnings update

   24h Move

   +0.3%

   FDA accepted the RASONQUE NDA for previously treated metastatic pancreatic cancer amid Phase 3 progress.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

breakthrough therapy designation, treatment-naïve, interstitial lung disease, cyp3a, +1 more

5 terms

breakthrough therapy designation regulatory

"the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation"

A breakthrough therapy designation is a regulatory fast-track given to a drug or treatment that shows early signs of providing a major improvement over existing options for a serious condition. Think of it as a VIP lane that can speed up development and more intensive guidance from regulators, which matters to investors because it can shorten time to market, reduce development risk and potentially increase a company’s value — though it does not guarantee approval.

treatment-naïve medical

"patients with treatment-naïve RAS mutant metastatic PDAC"

Patients described as treatment-naïve have not previously received the therapy being studied or other prior treatments for the same condition, so their bodies are ‘untouched’ by those drugs. For investors, this matters because results in a treatment-naïve group show how a therapy performs without prior drug effects, influence trial design and regulatory labeling, and help estimate the size and profile of the initial market—like testing a new seed in a garden that has never been treated before.

interstitial lung disease medical

"Interstitial Lung Disease (ILD)/Pneumonitis"

A group of lung conditions that cause inflammation and scarring of the thin tissue between the air sacs, which makes it harder for oxygen to pass into the blood; imagine the lungs’ fine filters becoming stiff and less effective. Investors care because reports of interstitial lung disease can affect a drug’s safety profile, trigger regulatory warnings or label changes, and shift demand for treatments or create liability risks that influence a company’s valuation.

cyp3a technical

"Strong CYP3A Inhibitors with P-gp Inhibition"

CYP3A is a group of liver enzymes that act like the body’s chemical processing machines, breaking down many medicines and other foreign substances so they can be removed. Investors care because drugs that are processed by CYP3A can interact with other drugs or require special dosing, affecting safety, regulatory approval, sales potential, and labeling; unexpected metabolism issues can materially change a drug’s market value.

p-gp technical

"Strong CYP3A Inhibitors with P-gp Inhibition"

P-gp is a pump-like protein on the surface of many cells that actively pushes a wide range of drugs and chemicals out of cells, influencing how much of a medicine is absorbed, reaches the brain, or stays at a target site. For investors, P-gp matters because its activity can make a drug less effective, change dosing or side effects, create drug interactions, and lead to extra testing or labeling that affects development cost and marketability—like a gatekeeper that can block a drug's path to success.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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• Company receives third Breakthrough Therapy Designation for RASONQUE and fifth across its portfolio of RAS(ON) inhibitors, further highlighting its differentiated strategy for developing innovative medicines for patients with RAS-addicted cancers
  

REDWOOD CITY, Calif., Sept. 14, 2026 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a global, commercial-stage oncology company dedicated to discovering, developing and delivering innovative medicines for patients with RAS-addicted cancers, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to RASONQUE (daraxonrasib), the company’s RAS(ON) multi-selective inhibitor, for treatment-naïve metastatic pancreatic adenocarcinoma (PDAC) in combination with gemcitabine and nab-paclitaxel (GnP), a multiagent chemotherapy regimen widely used in treating patients with PDAC. RASONQUE was recently approved by the U.S. FDA for the treatment of adult patients with metastatic PDAC who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.

The Breakthrough Therapy Designation is based on data from patients with treatment-naïve RAS mutant metastatic PDAC who received RASONQUE in combination with GnP in the open-label, multicenter Phase 1/2 RMC-GI-102 trial. In this cohort, RASONQUE in combination with GnP showed encouraging preliminary antitumor activity and a manageable safety profile that was consistent with the known safety profiles previously observed for both RASONQUE and GnP. These data informed the design of RASolute 303, the ongoing global Phase 3 trial evaluating RASONQUE as monotherapy and in combination with GnP versus GnP alone in patients with previously untreated metastatic PDAC, independent of tumor RAS genotype. The use of RASONQUE in combination with chemotherapy for treatment-naïve metastatic PDAC remains investigational with safety and efficacy not yet established.

“This Breakthrough Therapy Designation underscores the significant unmet need among patients with previously untreated metastatic pancreatic adenocarcinoma and recognizes the importance of advancing new treatment options earlier in their treatment journey,” said Alan Sandler, M.D., chief development officer of Revolution Medicines. “RASONQUE monotherapy demonstrated compelling clinical benefit in the RASolute 302 trial, leading to FDA approval for patients with previously treated metastatic pancreatic adenocarcinoma or those who are not candidates for multiagent systemic therapy. Data from the RMC-GI-102 study have now shown the therapeutic potential of RASONQUE in combination with GnP, a commonly used multiagent systemic therapy, in treatment-naïve patients. Together with our other ongoing studies, these findings reflect our deep commitment to advancing a broad RAS(ON) approach for patients with some of the most difficult-to-treat cancers.”

Breakthrough Therapy Designation is intended to expedite the development and review of potential new medicines designed to treat serious conditions and address significant unmet medical needs. Pursuant to FDA guidelines, the medicine needs to have shown preliminary clinical evidence that demonstrates substantial improvement on a clinically significant endpoint over available medicines.

About Pancreatic Adenocarcinoma (PDAC)
Pancreatic adenocarcinoma, or PDAC, is the most common form of pancreatic cancer and among the most challenging malignancies. Approximately 55,000 people are diagnosed with PDAC in the U.S. each year, and more than 50,000 die from the disease with current standard of care.^1,2 Because early-stage pancreatic cancer often causes few or no symptoms, approximately 80% of patients are diagnosed after the disease has spread, when treatment options are more limited. For patients with metastatic PDAC, the five-year relative survival rate is approximately 3% in the U.S.^3.4

About RASONQUE^TM (daraxonrasib)
RASONQUE (daraxonrasib) is an oral, RAS(ON) multi-selective, noncovalent, tri-complex inhibitor (TCI), approved by the U.S. FDA for the treatment of adult patients with metastatic pancreatic adenocarcinoma (PDAC) who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.⁵ RASONQUE is being investigated through a global Phase 3 registrational program in patients with PDAC and metastatic RAS mutant non-small cell lung cancer (NSCLC). Outside the U.S., RASONQUE is an investigational agent that has not been approved by any regulatory authority.

U.S. FDA APPROVED INDICATION
RASONQUE is indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.

IMPORTANT SAFETY INFORMATION FOR U.S. APPROVED INDICATION
RASONQUE is associated with the following Warnings and Precautions: Dermatologic and Soft Tissue Toxicity, Stomatitis and Oral Disorders, Diarrhea, Gastrointestinal Perforation, Interstitial Lung Disease (ILD)/Pneumonitis, and Embryo-Fetal Toxicity.

WARNINGS AND PRECAUTIONS

Dermatologic and Soft Tissue Toxicity
RASONQUE can cause dermatologic toxicity, which may be severe. Clinical manifestations included, but were not limited to, rash, pruritus, paronychia, dry skin, and skin fissures. In clinical trials of patients with pancreatic adenocarcinoma, dermatologic toxicity occurred in 86% of patients treated with RASONQUE, of which 10% were Grade 3.

Monitor patients who develop dermatologic or soft tissue toxicities while receiving RASONQUE. Initiate prophylactic measures (e.g., topical corticosteroids, emollient creams, sunscreen, oral antibiotics) prior to the first dose of RASONQUE to reduce the risk of moderate to severe dermatologic reactions. Advise patients to limit sun exposure while taking RASONQUE. Initiate supportive measures (e.g., oral corticosteroids) as clinically indicated, and consider dermatologic consultation. Withhold, reduce the dose, or permanently discontinue RASONQUE based on severity.

Stomatitis and Oral Disorders
RASONQUE can cause stomatitis, including mouth ulcers and oral mucositis. In clinical trials of patients with pancreatic adenocarcinoma, stomatitis occurred in 57% of patients, of which 9% were Grade 3.

Monitor patients for signs and symptoms of stomatitis while receiving RASONQUE. Initiate a steroid-containing mouthwash for treatment of stomatitis and administer other topical treatments (e.g., chlorhexidine mouthwash, 2% lidocaine viscous) as clinically indicated. Withhold, reduce the dose, or permanently discontinue RASONQUE based on severity.

Diarrhea
RASONQUE can cause diarrhea. In clinical trials of patients with pancreatic adenocarcinoma, diarrhea occurred in 63% of patients, of which 6% were Grade 3.
If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue RASONQUE based on severity.

Gastrointestinal Perforation
RASONQUE can cause gastrointestinal perforation. In clinical trials of patients with pancreatic adenocarcinoma, gastrointestinal perforation occurred in 0.9% of patients treated with RASONQUE, of which 0.5% were Grade 3, one event was Grade 4, and one event was fatal.

Monitor patients for gastrointestinal perforation. Withhold RASONQUE if gastrointestinal perforation is suspected. Reduce the dose or permanently discontinue RASONQUE if no other potential causes of gastrointestinal perforation are identified.

Interstitial Lung Disease (ILD)/Pneumonitis
RASONQUE can cause interstitial lung disease or pneumonitis. In clinical trials of patients with pancreatic adenocarcinoma, ILD/pneumonitis occurred in 2.4% of patients treated with RASONQUE, of which 0.9% were Grade 3, and one event was fatal.

Monitor patients for new or worsening pulmonary symptoms. Withhold RASONQUE if ILD/pneumonitis is suspected. Reduce the dose or permanently discontinue RASONQUE if no other potential causes of ILD/pneumonitis are identified.

Embryo-Fetal Toxicity
Based on findings in animals, RASONQUE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with RASONQUE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with RASONQUE and for 1 week after the last dose.

ADVERSE REACTIONS
Serious adverse reactions occurred in 30% of patients treated with RASONQUE. Serious adverse reactions occurring in ≥ 2% of patients treated with RASONQUE were diarrhea (3.7%), pyrexia (3.3%), sepsis (2.9%), fatigue (2.1%), and hemorrhage (2.1%).

Adverse reactions leading to permanent discontinuation of RASONQUE occurred in 2.9% of patients, including two patients who discontinued due to rash (0.8%).

The most common (≥ 20%) adverse reactions in patients treated with RASONQUE were rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.

DRUG INTERACTIONS

• Strong CYP3A Inhibitors with P-gp Inhibition: Avoid concomitant use.
• Strong CYP3A Inhibitors without P-gp Inhibition: Reduce RASONQUE dosage.
• Moderate CYP3A Inhibitors with or without P-gp Inhibition: Reduce RASONQUE dosage.
• P-gp Inhibitors: Reduce RASONQUE dosage.
• Cyclosporine A: Avoid concomitant use.
• Strong CYP3A Inducers: Avoid concomitant use. Increase RASONQUE dosage if concomitant use cannot be avoided.
• Moderate CYP3A Inducers: Increase RASONQUE dosage.
• P-gp Substrates: Take at least 4 hours apart from RASONQUE.

PROPHYLACTIC MEASURES
When initiating RASONQUE and throughout treatment, prophylactic and concomitant medications are recommended to reduce the risk of dermatologic reactions:

• administer a topical corticosteroid (applied to the face and chest) and emollient creams;
• advise patients to limit sun exposure and use broad-spectrum sunscreen (SPF 30 or higher); and
• consider prophylactic oral antibiotics (e.g., doxycycline or minocycline).
  

Please see U.S. Full Prescribing Information for RASONQUE

About Revolution Medicines, Inc.
Revolution Medicines is a global, commercial-stage oncology company dedicated to discovering, developing and delivering innovative medicines for patients with RAS-addicted cancers. Leveraging its differentiated RAS(ON) tri-complex inhibitor platform, the company is advancing a broad, integrated portfolio of oral RAS(ON) inhibitors designed to directly target the active, cancer-driving state of RAS. Founded on rigorous scientific inquiry and a willingness to challenge long-held assumptions, Revolution Medicines is committed to changing the trajectory of disease for patients with RAS-addicted cancers worldwide. For more information, visit www.revmed.com and follow Revolution Medicines on LinkedIn, X (Twitter) and Instagram.

Forward-Looking Statements 

This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding the broad potential of RAS(ON) inhibition; treatment practices; the company’s regulatory interactions and the potential for Breakthrough Therapy Designation to expedite the development and review of new medicines; reactions to RASONQUE; and progression of clinical studies and findings from these studies, including the tolerability, safety, and potential efficacy of the company's candidates being studied.

Forward-looking statements are typically, but not always, identified by the use of words such as "aims," "anticipate," "believe," "estimate," "expect," "plan," "potential," "project," "up to," "will" and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause the company's development programs, future results, performance, or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including the company's programs' development stages, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company's ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company's capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company's business of global events, such as international conflicts or global pandemics. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the "SEC") on August 5, 2026, and its future periodic reports to be filed with the SEC. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances, or to reflect the occurrence of unanticipated events.

Revolution Medicines Media & Investor Contacts 

Media
media@revmed.com  

Investors
investors@revmed.com 

References

¹ Oracle CancerMPact Patient Metrics, Stage IV newly incident + recurrent from earlier stages. Accessed July 2026.
² Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820
³ Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A. Pancreatic cancer: Advances and challenges. Cell. 2023;186(8):1729-1754. doi:10.1016/j.cell.2023.02.014
⁴ American Cancer Society. Survival Rates for Pancreatic Cancer. Available at: https://www.cancer.org/cancer/types/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html. Accessed September 2026.
⁵ RASONQUE (daraxonrasib) Prescribing Information. Redwood City, CA: Revolution Medicines, Inc.; August 2026.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What patient population is covered by the new Breakthrough Therapy Designation for RASONQUE?

The Breakthrough Therapy Designation applies to treatment-naïve metastatic pancreatic adenocarcinoma (PDAC) when RASONQUE is used in combination with gemcitabine and nab-paclitaxel, a multiagent chemotherapy regimen commonly used in PDAC.

How does the Breakthrough Therapy Designation differ from RASONQUE’s current U.S. approval?

RASONQUE is currently FDA approved for adult patients with metastatic PDAC who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. The new designation covers its investigational use in first-line metastatic PDAC in combination with gemcitabine and nab-paclitaxel, where safety and efficacy have not yet been established.

What is the purpose of FDA Breakthrough Therapy Designation in this context?

Breakthrough Therapy Designation is intended to expedite development and review of potential new medicines for serious conditions that address significant unmet medical needs. The medicine must show preliminary clinical evidence of substantial improvement on a clinically significant endpoint over available therapies.

What key clinical trial is now evaluating RASONQUE in previously untreated metastatic PDAC?

The ongoing global Phase 3 trial RASolute 303 is evaluating RASONQUE as monotherapy and in combination with gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel alone in patients with previously untreated metastatic PDAC, independent of tumor RAS genotype.

What are the most common adverse reactions reported with RASONQUE in pancreatic adenocarcinoma trials?

The most common (≥20%) adverse reactions were rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. Serious adverse reactions occurred in 30% of patients, with diarrhea, pyrexia, sepsis, fatigue, and hemorrhage each occurring in ≥2%.

Which major drug interaction categories are highlighted for RASONQUE?

RASONQUE has interactions with strong and moderate CYP3A inhibitors and inducers, P-gp inhibitors and substrates, and cyclosporine A. The guidance includes avoiding some combinations, reducing RASONQUE dosage with certain inhibitors, increasing dosage with inducers, and separating administration from P-gp substrates by at least 4 hours.