Dana-Farber Cancer Institute

Center for RAS Therapeutics Clinical Trials and Research

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    857-215-4727

    Our Track Record

    One of the key priorities of our center is to provide access to new therapies for RAS-driven cancers through clinical trial participation. Our portfolio of clinical trials for patients with KRAS-driven cancers is large and diverse, spanning different cancer types, different stages of disease, and different phases of clinical investigation. We also offer clinical trials that include combinations of therapies to further improve clinical outcomes with existing KRAS-targeted therapies.

    Dana-Farber investigators have been actively driving the development of new KRAS inhibitors, including the KRASG12C inhibitor adagrasib which is now FDA approved for patients with previously treated, KRASG12C-mutant lung cancer and KRASG12C-mutant colorectal cancer. There are also newer promising therapies like RMC-6236, a multi-selective RAS inhibitor which is being evaluated in a randomized phase 3 trial for patients with previously treated advanced pancreatic cancer.

    Research Areas of Interest

    Clinical Trials

    Dana-Farber boasts one of the largest portfolios of clinical trials investigating novel therapies for cancer patients, including therapies designed specifically for patients with KRAS-mutant cancers. The new RAS Center will work closely with investigators and with industry partners to identify the most promising clinical trials to open at Dana-Farber, based on mechanism of action, preclinical data, and the evolving treatment landscape.

    Focus on Drug Resistance

    While early therapeutic strategies targeting KRAS have shown promising results, some patients do not respond, and some patients who do respond eventually develop drug resistance leading to worsening disease. Dana-Farber investigators have played a major role in not only developing new targeted therapies but also discovering mechanisms of resistance to these therapies. Understanding why cancers become resistant is critical to developing new and more effective therapeutic strategies in the clinic.

    Investigators in the RAS Center have a special interest in resistance to RAS-targeted therapies. Our investigators published one of the first reports on resistance to KRASG12C inhibitors in the New England Journal of Medicine. In this study, resistant cancers from patients with KRASG12C-mutant lung and colorectal cancers were comprehensively profiled at the genomic level to discover multiple different mechanisms of resistance to adagrasib. We also recently reported the discovery of mechanisms of resistance to KRASG12C and KRASG12D inhibitors in clinical samples and preclinical models of pancreatic cancers. These and other studies have revealed fundamental insights into the biology of resistance and provided the scientific basis for developing new combinatorial strategies designed to overcome resistance.

    At present, there are no effective therapeutic strategies that can overcome resistance in KRAS-mutant cancers. Based on the latest research, we are pursuing many different combination strategies in the clinic, including combinations with cytotoxic chemotherapy, immunotherapy such as PD-1/PD-L1 inhibitors, and other targeted therapies such as Ras/MAPK pathway inhibitors and PRMT5 inhibitors. Our clinical trials may be industry sponsored and involve close collaboration with both the drug manufacturer and other academic sites. Other trials and studies may be investigator-initiated based on preclinical data developed at Dana-Farber using various cancer models such as patient-derived xenograft models, organoid models, or genetically engineered mouse models.

    Patients who are eligible for these clinical trials and research studies on resistance include those with RAS-mutant cancers who have previously received a RAS-targeted therapy. In some cases, these trials and studies may also include patients who have never received a RAS-targeted therapy to investigate whether a new approach may be able to prevent the development of resistance.

    Featured Clinical Trials

    KRASG12C

    Trial 20-098: NAUTIKA1: A Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Multiple Therapies in Biomarker-Selected Patients with Resectable Stages IB-III Non-Small Cell Lung Cancer
    Principal investigators: Narjust Florez, MD, and Ciaran McNamee, MD

    Trial 21-244: Phase 2 Trial of Adagrasib Monotherapy and in Combination with Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination with Pembrolizumab versus Pembrolizumab in Patients with Advanced NSCLC with KRASG12C Mutation (KRYSTAL-7)
    Principal investigator: Pasi Jänne, MD, PhD

    Trial 23-318: Phase 2 Trial of Combination Therapies with Adagrasib in Patients with Advanced NSCLC with KRASG12C Mutation (CA239-0010)
    Principal investigator: Pasi Jänne, MD, PhD

    Trial 20-261: Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 (Divarasib) as a Single Agent and in Combination with Other Anti-Cancer Therapies in Patients with Advanced or Metastatic Solid Tumors with KRASG12C Mutation
    Principal investigator: Jia Luo, MD

    Trial 24-524: Phase 3, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Divarasib versus Sotorasib or Adagrasib in Patients with Previously Treated KRASG12C-Positive Advanced or Metastatic NSCLC
    Principal investigator: Jia Luo, MD

    Trial 23-609: Phase 1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 in Combination with RMC-6236 in Participants with Advanced KRASG12C-Mutant Solid Tumors
    Principal investigator: Pasi Jänne, MD, PhD

    Trial 25-170: Phase 1/2 Open-Label, Dose Escalation, Dose Expansion and Cohort Expansion Study Evaluating the Safety, PK, and Clinical Activity of FMC-376 in Participants with KRASG12C-Mutated Locally Advanced Unresectable or Metastatic Solid Tumors
    Principal investigator: Jia Luo, MD

    KRASG12D

    Trial 23-571: Phase 1/1b, Multicenter, Open-Label, Study of RMC-9805 in Participants with Advanced KRASG12D-Mutant Solid Tumors
    Principal investigator: Kimmie Ng, MD, MPH

    Trial 24-255: Phase 1, Open-Label, Multicenter Study of INCB161734 in Participants with Advanced or Metastatic Solid Tumors with KRASG12D Mutation
    Principal investigator: Haeseong Park, MD, MPH

    Trial 22-574: Phase 1 Study of ASP3082 in Participants with Previously Treated Locally Advanced or Metastatic Solid Tumor Malignancies with KRASG12D Mutation
    Principal investigator: Pasi Jänne, MD, PhD

    Trial 24-621: A Phase 1a/1b Trial of LY3962673 in Participants with KRASG12D-Mutant Solid Tumors
    Principal investigator: Brandon Huffman, MD

    All KRAS mutations (panKRAS)

    Trial 22-297: A Multicenter Open-Label Study of RMC-6236 in Patients with Advanced Solid Tumors Harboring Specific Mutations in RAS
    Principal investigator: Brian Wolpin, MD, MPH

    Trial 24-325: Platform Study of RAS (ON) Inhibitors in Patients with Gastrointestinal Solid Tumors
    Principal investigator: Brian Wolpin, MD, MPH

    Trial 23-550: Phase 1 Open-Label, Dose-Escalation and Cohort Expansion Study of LUNA18 Monotherapy and Combination Therapy in Patients with Locally Advanced or Metastatic Solid Tumors
    Principal investigator: Haeseong Park, MD, MPH

    Trial 23-366: Phase 1, First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of KO-2806 when Administered as Monotherapy and in Combination Therapy in Adult Patients with Advanced Solid Tumors
    Principal investigator: Glenn Hanna, MD

    Trial 24-533: RASolute 302: A Phase 3 Multicenter, Open-label, Randomized Study of RMC-6236 versus Investigator’s Choice of Standard of Care Therapy in Patients with Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
    Principal investigator: Brian Wolpin, MD, MPH

    What to Expect From a Clinical Trial

    At Dana-Farber, your treatment team is based in one of our specialized disease centers for different cancer types. These include the Gastrointestinal Cancer Treatment Center, the Thoracic (Lung) Cancer Treatment Center, or the Gynecologic Oncology Program. You may be referred to our Center for Cancer Therapeutic Innovation (CCTI) which primarily conducts phase 1 trials of new drugs or drug combinations across different cancer types. If you participate in a CCTI phase 1 trial, your original team will still be very much involved in your care.

    When you come to Dana-Farber for a clinical trial, we will provide you with specific information about what your participation in the trial will entail. We will make sure that you, your family, and your treatment team understand all aspects of your involvement in the trial. Participation in a clinical trial is voluntary; it is always your choice whether you take part in the research or not.

    The staff at Dana-Farber are devoted to pursuing excellence in the safe conduct of clinical trials for cancer patients, with compassion and respect for everyone involved.