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Pancreatic Ductal AdenocarcinomaPhase 1NCT07898813

Daraxonrasib in Resectable PDAC

A Phase 1 study testing Daraxonrasib, Surgical Resection and Adjuvant Chemotherapy in people with Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

This Phase 1 interventional treatment study is evaluating oral daraxonrasib in participants with resectable pancreatic ductal adenocarcinoma. The study includes pre-surgery daraxonrasib treatment, surgery, adjuvant chemotherapy with or without radiation, optional adjuvant daraxonrasib, and follow-up. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Daraxonrasib, Surgical Resection and Adjuvant Chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesUnited States
Study dates
13 Apr 2027to 13 Aug 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The clinical, radiographic, and pathologic evidence support a diagnosis of pancreatic adenocarcinoma, with histology confirmatory for adenocarcinoma, adenosquamous carcinoma, or poorly differentiated carcinoma.
  • Subjects must be determined to meet the criteria for resectable pancreatic cancer based on National Comprehensive Cancer Network (NCCN) criteria at initial diagnosis (Table 2). Patients with borderline resectable, locally advanced, or metastatic disease are not eligible for this trial.
  • Resectability status
  • Resectable
  • Borderline resectable
  • Locally advanced
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  • Arterial
  • No arterial tumor contact (celiac axis (CA), superior mesenteric artery (SMA), or common hepatic artery (CHA))
  • Pancreatic head/uncinate process:
  • Solid tumor contact with CHA without extension to CA or hepatic artery bifurcation allowing for safe and complete resection and reconstruction.
  • Solid tumor contact with the SMA of ≤180°.
  • Solid tumor contact with variant arterial anatomy (eg, accessory right hepatic artery, replaced right hepatic artery, replaced CHA, and the origin of replaced or accessory artery) and the presence and degree of tumor contact should be noted if present, as it may affect surgical planning.
  • Pancreatic body/tail:
  • Solid tumor contact with the CA of ≤180°.
  • Head/uncinate process:
  • Solid tumor contact >180° with the SMA or CA.
  • Pancreatic body/tail:
  • Solid tumor contact of >180° with the SMA or CA.
  • Solid tumor contact with the CA and aortic involvement.
  • Venous -No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) OR ≤ 180° of contact without vein contour irregularity.
  • Solid tumor contact with the SMV or PV of >180°, contact of ≤180° with contour irregularity of the vein or thrombosis of the vein but with suitable vessel proximal and distal to the site of involvement allowing for safe and complete resection and vein reconstruction.
  • Solid tumor contact with the inferior vena cava (IVC). Not currently amenable to resection and primary reconstruction due to complete occlusion of SMV/PV
  • NCCN guideline definition of resectability status
  • Prospective determination of RAS mutation status is not required
  • Participants must be ≥ 18 years old
  • Participants must have an ECOG performance status of 0 or 1
  • Participants must have adequate organ and marrow function as defined as:
  • Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) or <2 x ULN in patients with Gilbert syndrome
  • AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
  • Creatinine Calculated estimated glomerular filtration rate ≥60 mL/min
  • Coagulation function PT/INR/PTT <1.5 x ULN, or ≤ 2 x ULN for those on anticoagulation
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 9 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.
  • Ability to swallow oral medications and willing to keep daily adherence record.
  • Ability to understand and the willingness to sign a written informed consent document
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Presence of metastatic disease
  • Requirement of pre-operative or neoadjuvant radiation therapy to primary pancreatic tumor as determined by multi-disciplinary tumor board.
  • Tumors with the following histologic features in addition to an adenocarcinoma component are excluded: neuroendocrine, undifferentiated with osteoclast like giant cells, acinar, hepatoid, medullary carcinomas.
  • Known BRAF activating mutation or gene rearrangement that is suggestive of resistance to daraxonrasib
  • Prior treatment with MAPK targeted therapy including pan-RAS, pan-KRAS, KRAS mutant allele specific, BRAF, MEK, or ERK inhibitors.
  • Treatment with any investigational agents within the last 14 days or 5 half-lives, whichever is shorter, from C1D1 of this trial drug. No prior treatment for pancreatic cancer is allowed.
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  • Has a left ventricular ejection fraction <50% within 4 weeks, symptomatic heart failure within 4 weeks, acute coronary syndrome within 6 months or medically uncontrolled hypertension (>160 mmHg systolic blood pressure or >100 diastolic blood pressure) based on average of 3 readings.
  • Prolonged QTc interval >470ms, averaged from 3 electrocardiograms (EKGs).
  • History of or active interstitial lung disease, pneumonitis, pulmonary fibrosis which required steroid treatment within 6 months.
  • Known or suspected gastrointestinal disorder which may hinder ability to take PO drug or hinder absorption
  • Requires treatment with systemic cyclosporine A or derivative
  • Has had consumption within the last 14 days or 5 half-lives, whichever is shorter, from C1D1 of this trial drug or requires ongoing consumption of P-gp or CYP3A inducers or inhibitor (See APPENDIX B)
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
  • Has a history of other cancers diagnosed or treated within last 3 years. Clinically insignificant cancers which require no significant treatment or tumors treated with definitive intent and with low risk of recurrence are not excluded. Discussion with sponsor investigator is encouraged.
  • Subject is unable or unwilling to participate in a study related procedure.
  • Has an active serious infection requiring systemic therapy
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Brandon Huffman, MD contact

(617) 667-8800

brandon_huffman@dfci.harvard.edu

United States2 sites

  • Brigham and Women's Hospital (BWH)

    Boston, Massachusetts, 02215

    Brandon Huffman, MD, brandon_huffman@dfci.harvard.edu

    Brandon Huffman, MD

  • Massachusetts Institute of Technology

    Boston, Massachusetts, 02215

    Brandon Huffman, MD

    Brandon Huffman, MD

Other trials in United States

About this study

Official title: Daraxonrasib in Resectable Pancreatic Ductal Adenocarcinoma

This Phase 1 interventional treatment study is evaluating oral daraxonrasib in participants with resectable pancreatic ductal adenocarcinoma. The study includes pre-surgery daraxonrasib treatment, surgery, adjuvant chemotherapy with or without radiation, optional adjuvant daraxonrasib, and follow-up. The protocol also includes research blood, stool, tissue, and de-identified data collection for correlative and future research.

Read the detailed description

This is a DF/HCC PI-sponsored Phase 1 interventional treatment trial in resectable pancreatic ductal adenocarcinoma. Participants are screened before starting treatment and then assigned to one of two protocol-defined cohorts that differ in the duration of neoadjuvant daraxonrasib before surgery. Study treatment includes oral daraxonrasib once daily during 28-day cycles before surgery, followed by surgical resection, adjuvant chemotherapy with or without radiation per institutional standard and physician discretion, and optional adjuvant daraxonrasib for up to 32 cycles (24 months) after completion of adjuvant therapy. The study includes safety monitoring, tumor assessments, laboratory testing, collection of archival tumor tissue, research blood and stool, and sharing of de-identified data and biospecimens with outside collaborators for analysis and future research. Planned accrual is 30 participants over 24 months, with post-treatment follow-up at least every 6 months for up to 5 years.

Being tested
Daraxonrasib, Surgical Resection, Adjuvant Chemotherapy, Adjuvant Radiation Therapy
Keywords
Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer, Resectable Pancreatic Ductal Adenocarcinoma, daraxonrasib, RMC-6236, resectable PDAC, surgery, adjuvant chemotherapy, radiation therapy, targeted therapy, genetic studies
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaraxonrasibDrug

    Also called RMC-6236

    Oral study drug taken once daily in 28-day cycles at a predetermined dose before surgery, and optionally again in the adjuvant setting after completion of adjuvant therapy.

  • Surgical ResectionProcedure or surgery

    Protocol-planned surgery performed after neoadjuvant daraxonrasib treatment and surgical planning.

  • Adjuvant ChemotherapyDrug

    Post-surgery chemotherapy administered per institutional standard and investigator/physician discretion.

  • Adjuvant Radiation TherapyRadiation

    Post-surgery radiation therapy may be given with adjuvant chemotherapy according to institutional standard and investigator/physician discretion.

Study groups in NCT07898813
Study groupRoleWhat they receive
Cohort A Perioperative DaraxonrasibExperimentalParticipants receive oral daraxonrasib once daily at a predetermined dose for 6 weeks before surgery, followed by a surgical planning interval, surgical resection, adjuvant chemotherapy with or without radiation per institutional standard and investigator discretion, and optional adjuvant daraxonrasib after completion of adjuvant therapy.
Receives: Drug: Daraxonrasib; Procedure: Surgical Resection; Drug: Adjuvant Chemotherapy; Radiation: Adjuvant Radiation Therapy
Cohort B Perioperative DaraxonrasibExperimentalParticipants receive oral daraxonrasib once daily at a predetermined dose for 12 weeks before surgery, followed by a surgical planning interval, surgical resection, adjuvant chemotherapy with or without radiation per institutional standard and investigator discretion, and optional adjuvant daraxonrasib after completion of adjuvant therapy.
Receives: Drug: Daraxonrasib; Procedure: Surgical Resection; Drug: Adjuvant Chemotherapy; Radiation: Adjuvant Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Successful Receipt of Surgery Rate

    Proportion of participants who complete neoadjuvant darazonrasib therapy and then attempt surgery.

    Measured: After 6- or 12-weeks of neoadjuvant therapy

Secondary outcomes (5)

  1. R0 Resection Rate

    Proportion of participants who undergo surgery after completing neoadjuvant darazonrasib therapy and achieve negative margin (R0) resection status.

    Measured: After 6- or 12-weeks of neoadjuvant therapy

  2. Objective Response Rate (ORR)

    ORR is defined as the proportion of participants achieving complete response (CR) or partial response (PR) on neoadjuvant darazonrasib therapy. Per RECIST 1.1 criteria for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

    Measured: After 6- or 12-weeks of neoadjuvant therapy

  3. Disease Control Rate (DCR)

    DCR is defined as the proportion of participants achieving CR, PR or stable disease (SD) on neoadjuvant darazonrasib therapy. Per RECIST 1.1 criteria: SD is not achieving PR or experiencing disease progression (PD). PD per RECIST 1.1 for target lesions is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

    Measured: After 6- or 12-weeks of neoadjuvant therapy

  4. Pathologic Response Rate

    Proportion of participants who achieve pathologic response defined as tumor regression of grades 0 or 1 in all participants who underwent resection based on evaluation of the resected pancreatic tumor specimen by an experienced pathologist as reported according to College of American Pathologist guidelines (2012).

    Measured: After 6- or 12-weeks of neoadjuvant therapy

  5. Grade 3-4 Adverse Event Rate

    Proportion of participants who experience a grade 3 or 4 adverse event on neoadjuvant darazonrasib therapy as measured by CTCAE version 5.

    Measured: After 6- or 12-weeks of neoadjuvant therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2026
  2. Study start13 Apr 2027 (estimated)
  3. Primary completion17 Feb 2029 (estimated)
  4. Study completion13 Aug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07898813
Sponsor's protocol ID
26-554
Status last verified
Oct 2026
First submitted
20 Oct 2026
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daraxonrasib, Surgical Resection and Adjuvant Chemotherapy in people with Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Brandon Huffman, MD ((617) 667-8800, brandon_huffman@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Successful Receipt of Surgery Rate (time frame: After 6- or 12-weeks of neoadjuvant therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07898813.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

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