Revolution Medicines Presents Phase 1/2 Clinical Data for Zoldonrasib Combination Regimens in Patients with RAS G12D Metastatic Pancreatic Cancer at ESMO Gastrointestinal Cancers Congress 2026 

Rhea-AI Summary

Revolution Medicines (Nasdaq: RVMD) reported Phase 1/2 data for zoldonrasib combinations in RAS G12D metastatic pancreatic cancer at ESMO GI 2026.

First-line zoldonrasib plus chemotherapy showed ORR up to 82%, while zoldonrasib plus daraxonrasib in pretreated patients showed ORR of 47–50%, supporting pivotal Phase 3 RASolute 305 and 309 trials.

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

Positive

• First-line zoldonrasib plus mFFX ORR 82% and DCR 96%
• First-line zoldonrasib plus GnP ORR 61% and DCR 90%
• Second-line zoldonrasib plus daraxonrasib ORR 50% and DCR 97%
• Third-line-plus zoldonrasib plus daraxonrasib ORR 47% and DCR 90%
• Second-line zoldonrasib plus daraxonrasib median PFS 9.6 months
• Data underpin ongoing Phase 3 RASolute 305 and planned Phase 3 RASolute 309

Negative

• Grade ≥3 TRAEs in 61% with zoldonrasib plus mFFX
• Grade ≥3 TRAEs in 80% with zoldonrasib plus GnP
• Grade ≥3 TRAEs in 35% with zoldonrasib plus daraxonrasib
• Common severe events include decreased neutrophils, anemia, fatigue and rash

What This Means

This announcement adds robust Phase 1/2 efficacy and durability signals for zoldonrasib combinations...

Analysis

This announcement adds robust Phase 1/2 efficacy and durability signals for zoldonrasib combinations in metastatic PDAC, building on prior RASolute data. Investors may watch how Phase 3 designs evolve and whether safety, insider selling, or trial execution introduce new risks.

Key Figures

Enrollment mFFX arm: 41 patients Enrollment GnP arm: 40 patients ORR mFFX arm: 82% ORR (95% CI: 60–95) +5 more

8 metrics

Enrollment mFFX arm 41 patients Zoldonrasib plus modified FOLFIRINOX, first-line PDAC

Enrollment GnP arm 40 patients Zoldonrasib plus gemcitabine/nab-paclitaxel, first-line PDAC

ORR mFFX arm 82% ORR (95% CI: 60–95) Zoldonrasib plus mFFX, first-line RAS G12D PDAC

ORR GnP arm 61% ORR (95% CI: 42–78) Zoldonrasib plus GnP, first-line RAS G12D PDAC

ORR 2L cohort 50% ORR (95% CI: 31–69) Zoldonrasib plus daraxonrasib, second-line PDAC (N=30)

Median PFS 2L 9.6 months (95% CI: 7.1–NE) Zoldonrasib plus daraxonrasib, second-line PDAC

Median PFS 3L+ 7.6 months (95% CI: 4.6–10.5) Zoldonrasib plus daraxonrasib, third-line+ PDAC

Grade ≥3 TRAEs combo 35% of patients Zoldonrasib plus daraxonrasib, previously treated PDAC

Peers on Argus

At publication, biotech peers showed mixed, mostly modest moves, with MRNA and B...

1 Up

At publication, biotech peers showed mixed, mostly modest moves, with MRNA and BPMC up and MDGL, ROIV down. Only one momentum peer screened, so RVMD’s setup looked more stock‑specific than sector‑driven.

Previous Clinical trial Reports

5 past events · Latest: Jun 24 (Neutral)

Same Type Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Jun 24	Data preview	Neutral	+5.0%	Preview of upcoming RAS(ON) pancreatic cancer data at ESMO GI 2026.
Jun 23	Phase 3 initiation	Positive	+2.2%	Start of RASolute 305 Phase 3 trial of zoldonrasib plus chemotherapy in PDAC.
May 31	Phase 3 results	Positive	+3.9%	Pivotal RASolute 302 daraxonrasib data showing survival benefit in treated PDAC.
May 06	NEJM publication	Positive	-5.7%	NEJM Phase 1/2 daraxonrasib data and support for RASolute 302 initiation.
Apr 21	Conference data	Positive	-4.4%	Updated Phase 1/2 daraxonrasib first‑line PDAC data ahead of AACR 2026.

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

Pattern Detected

Clinical trial announcements have triggered several strong moves, with three positive and two negative reactions over recent events.

Historical Comparison

+0.2% avg move · Over five recent clinical trial headlines, RVMD’s stock typically showed only a small average move, ...

clinical trial

+0.2%

Average Historical Move clinical trial

Over five recent clinical trial headlines, RVMD’s stock typically showed only a small average move, with both sharp gains and pullbacks. This zoldonrasib combination update fits that pattern of impactful but variably priced trial news.

Recent history shows steady progression from early daraxonrasib studies through pivotal RASolute 302 and now zoldonrasib combinations advancing toward Phase 3 strategies in both first‑ and later‑line RAS‑mutant pancreatic cancer.

Regulatory & Risk Context

Short Interest: 5.94%

Short Interest

5.94% of float

0% 15% 30%+

low as of 2026-06-15 Days to cover: 4.31

Short positioning appears relatively low, suggesting only moderate short‑squeeze dynamics and a more typical volatility profile around major clinical or regulatory catalysts.

Key Terms

pdac, objective response rate, disease control rate, progression-free survival, +2 more

6 terms

pdac medical

"metastatic pancreatic ductal adenocarcinoma (PDAC)."

PDAC stands for pancreatic ductal adenocarcinoma, the most common and aggressive form of pancreatic cancer that starts in the pancreas’s duct cells. It matters to investors because PDAC represents a large unmet medical need with high patient mortality, driving intense drug development, clinical trial activity and potential regulatory milestones—like a critical, hard-to-fix engine part whose failure creates urgent demand for effective solutions, affecting a company’s valuation and risk profile.

objective response rate medical

"with an objective response rate (ORR) of 82% (95% confidence interval"

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

disease control rate medical

"and disease control rate (DCR) of 96% (95% CI: 77, 100)"

The disease control rate is the share of patients in a clinical trial whose cancer or condition either shrinks or stops getting worse for a specified period after treatment. Think of it like the percentage of people for whom a treatment hits pause or nudges back the problem rather than letting it progress; higher rates suggest the therapy can meaningfully limit disease, which matters to investors assessing a drug’s potential efficacy and commercial value.

progression-free survival medical

"Median progression-free survival (PFS) in the 2L cohort was 9.6 months"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

overall survival medical

"Median overall survival (OS) in the 2L cohort was not yet estimable"

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

treatment-related adverse events medical

"Grade 3 or greater treatment-related adverse events (TRAEs) occurred in 61%"

Treatment-related adverse events are harmful or unwanted health effects that doctors or regulators determine were caused by a drug, vaccine, device, or other medical therapy. Investors care because how often and how severe these side effects are can shape regulatory approval, labeling, sales potential and legal risk — similar to how product defects can stop or damage a company's ability to sell an item.

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

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REDWOOD CITY, Calif., July 02, 2026 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced results from two Phase 1/2 clinical trials evaluating zoldonrasib, its oral RAS(ON) G12D-selective covalent inhibitor, in combination regimens for patients with RAS G12D metastatic pancreatic ductal adenocarcinoma (PDAC). The results, which will be presented today in a proffered paper session at the 2026 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress, include zoldonrasib in combination with standard of care chemotherapy in previously untreated patients and zoldonrasib in combination with daraxonrasib, the company’s oral RAS(ON) multi-selective inhibitor, in previously treated patients.

“The Phase 3 RASolute 302 results provided clinical validation of RAS(ON) inhibition with daraxonrasib in second line metastatic pancreatic cancer and established a strong foundation for evaluating this therapeutic approach across additional RAS genotypes, treatment settings and combination strategies. The results presented at ESMO GI demonstrate compelling proof-of-concept for two zoldonrasib-based regimens in RAS G12D disease: combination with standard of care chemotherapy in previously untreated patients and a RAS(ON) inhibitor doublet with daraxonrasib in previously treated patients. Together, these findings are the foundation of two distinct Phase 3 strategies we are pursuing in previously untreated metastatic RAS G12D pancreatic cancer: the ongoing RASolute 305 trial evaluating zoldonrasib plus standard of care chemotherapy, and the planned RASolute 309 trial evaluating the combination of zoldonrasib plus daraxonrasib,” said Alan Sandler, M.D., chief development officer of Revolution Medicines.

Safety and Efficacy of Zoldonrasib Plus Chemotherapy in Patients with First Line RAS G12D Metastatic Pancreatic Cancer (Abstract #340O)

RMC-GI-102 (NCT06445062) is an ongoing Phase 1/2 trial evaluating zoldonrasib 1200 mg once daily in combination with investigator's choice of standard of care chemotherapy in patients with previously untreated metastatic RAS G12D PDAC. Investigator's choice of chemotherapy includes modified FOLFIRINOX (mFFX) or gemcitabine plus nab-paclitaxel (GnP). As of the February 8, 2026 data cutoff, the trial enrolled 41 patients in the zoldonrasib plus mFFX arm and 40 patients in the zoldonrasib plus GnP arm.

Zoldonrasib demonstrated a manageable safety and tolerability profile in combination with standard chemotherapy. The safety profile of zoldonrasib in combination with chemotherapy was broadly consistent with the established profiles of each respective chemotherapy regimen. Grade 3 or greater treatment-related adverse events (TRAEs) occurred in 61% of patients who received the zoldonrasib plus mFFX and 80% of patients who received zoldonrasib plus GnP. The most common Grade 3 or greater TRAEs with zoldonrasib plus mFFX were decreased neutrophil count (37%), anemia (12%), and platelet count decreased (7%). The most common Grade 3 or greater TRAEs with zoldonrasib plus GnP were decreased neutrophil count (35%), anemia (28%), and fatigue (25%). No Grade 5 TRAEs were reported in either arm. The mean dose intensity was 86% with zoldonrasib plus mFFX and 90% with the zoldonrasib plus GnP.

In the trial, zoldonrasib with chemotherapy showed compelling antitumor activity, with an objective response rate (ORR) of 82% (95% confidence interval [CI]: 60, 95) and disease control rate (DCR) of 96% (95% CI: 77, 100) in the mFFX population, and an ORR of 61% (95% CI: 42, 78) and DCR of 90% (95% CI: 74, 98) in the GnP population.

These preliminary safety and clinical activity data support the ongoing RASolute 305 pivotal trial (NCT07621718), a global, randomized, double-blind placebo-controlled Phase 3 clinical trial evaluating zoldonrasib plus investigator’s choice of standard of care chemotherapy compared with placebo plus investigator’s choice of chemotherapy in patients with previously untreated metastatic RAS G12D PDAC.

Safety and Efficacy of Zoldonrasib Plus Daraxonrasib in Patients with Second Line-Plus RAS G12D Metastatic Pancreatic Cancer (Abstract #341O)

RMC-9805-001 (NCT06040541) is a Phase 1 trial evaluating zoldonrasib 1200 mg once daily plus daraxonrasib 300 mg once daily in advanced solid tumors with RAS G12D mutations. As of the February 9, 2026 data cutoff, 60 patients with RAS G12D metastatic PDAC who had previously received one or more prior lines of therapy were treated with the combination.

Zoldonrasib plus daraxonrasib demonstrated a manageable safety and tolerability profile that was broadly consistent with the established profile of daraxonrasib monotherapy. Grade 3 or greater TRAEs occurred in 35% of patients who received the combination. Among TRAEs occurring in 10% or more of all patients, the most common Grade 3 or greater events were rash (12%), anemia (10%), and stomatitis/mucositis (7%). Few patients discontinued due to TRAES; 2% discontinued zoldonrasib and 5% discontinued daraxonrasib. The mean dose intensity was 88% for zoldonrasib and 76% for daraxonrasib.

The zoldonrasib plus daraxonrasib combination demonstrated compelling antitumor activity in patients with previously treated metastatic PDAC. In the second line cohort (2L) (N=30), the ORR was 50% (95% CI: 31–69) and DCR was 97% (95% CI: 83–100). Median progression-free survival (PFS) in the 2L cohort was 9.6 months (95% CI: 7.1–NE), with a 6-month PFS rate of 71%. Median overall survival (OS) in the 2L cohort was not yet estimable, with a 6-month OS rate of 89%. In the third line and beyond (3L+) cohort (N=30), the ORR was 47% (95% CI: 28–66) and DCR was 90% (95% CI: 74–98). Median PFS in the 3L+ cohort was 7.6 months (95% CI: 4.6–10.5), with a 6-month PFS rate of 59%. Median OS in the 3L+ cohort was 10.5 months (95% CI: 6.7–NE), with a 6-month OS rate of 82%.

These safety and clinical activity data support the planned pivotal global, Phase 3 RASolute 309 clinical trial of zoldonrasib plus daraxonrasib versus GnP in patients with previously untreated RAS G12D metastatic PDAC.

About Pancreatic Cancer and Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. Pancreatic ductal adenocarcinoma, or PDAC, is the most common form of pancreatic cancer. Due to the lack of early symptoms and effective detection methods, approximately 80% of patients are diagnosed with advanced or metastatic disease. PDAC is the most commonly RAS-driven malignancy of all major cancers, with more than 90% of patients having tumors that harbor RAS mutations.¹ RAS G12D is the most prevalent RAS mutation subtype in PDAC, occurring in 40% of patients, and has been associated with poorer outcomes than RAS wild-type disease and certain other RAS-mutant subgroups.^1-4

About Zoldonrasib
Zoldonrasib is an investigational, oral RAS(ON) G12D-selective covalent tri-complex inhibitor. RAS G12D is the most prevalent RAS mutation, accounting for 29% of all RAS cancers.¹ Across tumor types, approximately 61,000 new patients with RAS G12D cancers are estimated each year in the U.S., and no targeted therapy is currently approved for these patients.⁵ Zoldonrasib is currently being evaluated as a monotherapy and in combination with other therapies, including with Revolution Medicines’ RAS(ON) multi-selective inhibitor daraxonrasib (RMC-6236), as well as standard of care regimens in lung and gastrointestinal cancers.

About Daraxonrasib
Daraxonrasib is an investigational, oral RAS(ON) multi-selective, non-covalent tri-complex inhibitor. The U.S. Food and Drug Administration (FDA) granted daraxonrasib Breakthrough Therapy Designation and Orphan Drug Designation for the treatment of patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) harboring G12 mutations. In addition, daraxonrasib was selected for the FDA Commissioner’s National Priority Voucher pilot program, which is intended to accelerate the development and review of therapies aligned with U.S. national health priorities.

Daraxonrasib is designed to target cancers driven by a broad range of common RAS genotypes, including PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer. Daraxonrasib is being advanced through a global Phase 3 registrational program comprising four trials, including the completed RASolute 302 trial and three additional trials in patients with PDAC and metastatic RAS mutant NSCLC.

About Revolution Medicines, Inc.
Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor; and RMC-5127, a RAS(ON) G12V-selective inhibitor, are currently in clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn.

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 our development strategy, including in RAS G12D pancreatic cancer; the potential of our product candidates for RAS(ON) inhibition, including in pancreatic cancer; the ability of daraxonrasib or zoldonrasib to improve patient outcomes; planned and ongoing clinical studies; and potential efficacy of the company’s product candidates being studied.

Forward-looking statements are typically, but not always, identified by the use of words such as “anticipate,” "estimate," "plan," “potential,” “proof-of-concept,” “pursuing,” "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 the 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’ Annual Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on May 6, 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 Contact:
media@revmed.com
investors@revmed.com

References

¹ Lee JK, Sivakumar S, Schrock AB, et al. Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors. NPJ Precis Oncol. 2022;6(1);91. doi:10.1038/s41698-022-00334-z
² Yousef, A., Yousef, M., Chowdhury, S. et al. Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma. NPJ Precis Oncol. 2024;8:27. https://doi.org/10.1038/s41698-024-00505-0
³ Qian ZR, Rubinson DA, Nowak JA, et al. Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. JAMA Oncol. 2018;4(3):e173420. doi:10.1001/jamaoncol.2017.3420
⁴ Norton C, Shaw MS, Rubnitz Z, et al. KRAS Mutation Status and Treatment Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma. JAMA Netw Open. 2025;8(1):e2453588. doi:10.1001/jamanetworkopen.2024.53588
⁵ Estimated using tumor mutation frequencies from Foundation Medicine Insights March 2022 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2023.

FAQ

What Phase 1/2 zoldonrasib data did Revolution Medicines (RVMD) present at ESMO GI 2026?

Revolution Medicines presented Phase 1/2 data for zoldonrasib combination regimens in RAS G12D metastatic pancreatic cancer. According to Revolution Medicines, results cover first-line zoldonrasib plus chemotherapy and zoldonrasib plus daraxonrasib in previously treated patients, informing pivotal Phase 3 RASolute 305 and 309 strategies.

What were the objective response rates for RVMD zoldonrasib plus chemotherapy in first-line RAS G12D metastatic pancreatic cancer?

Zoldonrasib plus modified FOLFIRINOX showed an objective response rate of 82%, while zoldonrasib plus gemcitabine/nab-paclitaxel showed 61%. According to Revolution Medicines, disease control rates were 96% and 90% respectively, supporting the ongoing Phase 3 RASolute 305 trial in previously untreated RAS G12D pancreatic cancer.

How effective was RVMD zoldonrasib plus daraxonrasib in previously treated RAS G12D metastatic pancreatic cancer?

Zoldonrasib plus daraxonrasib produced objective response rates of 50% in second line and 47% in third line-plus cohorts. According to Revolution Medicines, median progression-free survival reached 9.6 months in second line and 7.6 months in third line-plus, with disease control rates of 97% and 90% respectively.

What safety profile was reported for RVMD zoldonrasib combination regimens in RAS G12D metastatic pancreatic cancer?

Zoldonrasib plus chemotherapy had Grade 3 or higher treatment-related adverse events in 61% and 80% of patients, depending on regimen. According to Revolution Medicines, the daraxonrasib combination showed Grade 3 or higher events in 35% of patients, with few treatment discontinuations and no Grade 5 treatment-related events reported.

How do the new zoldonrasib data impact RVMD’s Phase 3 RASolute 305 and 309 trials?

The Phase 1/2 results provide clinical support for RVMD’s planned and ongoing Phase 3 programs in RAS G12D pancreatic cancer. According to Revolution Medicines, first-line chemotherapy combination data support RASolute 305, while doublet inhibition data support the planned RASolute 309 trial versus gemcitabine/nab-paclitaxel.

What progression-free and overall survival outcomes were reported for RVMD zoldonrasib plus daraxonrasib in RAS G12D pancreatic cancer?

Median progression-free survival was 9.6 months in second line and 7.6 months in third line-plus cohorts. According to Revolution Medicines, median overall survival was not estimable in second line and 10.5 months in third line-plus, with six-month overall survival rates of 89% and 82% respectively.