Dana-Farber Cancer Institute

Center for RAS Therapeutics Clinical Trials and Research

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    Contact the Center for RAS Therapeutics

    857-215-4727

    For provider referrals or clinical trial questions, email: DFCIRASReferrals@dfci.harvard.edu

    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 25-112: A Phase 1/1b, Open-label, Multicenter, Dose Escalation and Dose Optimization Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of KQB365 as Monotherapy and in Combination with Anti-cancer Agents in Participants with Advanced Solid Malignancies with KRAS G12S or G12C mutations
    Principal Investigator: Kimmie Ng, MD, MPH

    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

    Trial 26-407: A Phase III, Randomized, Open-label Study Evaluating the Efficacy and Safety of Divarasib Compared with Investigator's Choice of Immunotherapy or Observation in Patients with Respected Stage II-III KRAS G12C-Positive Non-Small Cell Lung Cancer
    Principal Investigator: Narjust Florez, MD

    Trial 26-413: Solid tumor Study for Long term Treatment of Cancer Patients Who Have Participated in BMS-Parent Studies Investigating Adagrasib (BMS-9865) 
    Principal Investigator: Pasi Jänne, MD, PhD

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

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

    Trial 25-206: A Phase I/II Dose-Escalation and Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-7035 as a Single Agent and in Combination With Other Anti-Cancer Therapies in Patients With Advances Solid Tumors With a KRAS G12D Mutation
    Principal Investigator: Haeseong Park, MD, MPH

    Trial 25-552: An Open-label, Phase 1, Multi-Center Master Protocol to Evaluate the Safety and Preliminary Anti-Tumor Activity of TCR-engineered T cells Recognizing KRAS Mutations in Adult Subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors
    Principal Investigator: Jennifer Marks, MD

    Trial 26-273: A Randomized, Double-Blind, Phase 3 Study of Chemotherapy With or Without INCB161734 in Previously Untreated, KRAS G12D Mutated Metastatic Pancreatic Ductal Adenocarcinoma (DAWN-303)
    Principal Investigator: Brandon Huffman, MD

    Trial 26-422: A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and with Cetuximab, in Patients with Metastatic KRAS G12D-Mutated Pancreatic Cancer (TARGET-D 201) 
    Principal Investigator: Kimberly Perez, MD

    Other RAS mutations (panKRAS or panRAS)

    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 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

    Trial 25-110: 3263-001: A Phase 1/1b Multiple Cohort Trial of ALTA3263 in Patients With Advanced Solid Tumors With KRAS Mutations
    Principal Investigator: Haeseong Park, MD, MPH

    Trial 25-371: A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG462 in Combination with Other Agents in Patients with Pancreatic Cancer with MTAP Loss; and Pancreatic or Non-Small Cell Lung Cancer with MTAP Loss and RAS Mutation
    Principal Investigators: Kim Perez, MD and Jia Luo, MD

    Trial 25-698: An Open-Label, Multicenter, Phase 1 Trial to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of TLN-372 as a Single Agent and in Combination with Other Anti-Tumor Agents, in Patients with Advanced KRAS Mutant Solid Tumors
    Principal Investigator: Alice Shaw, MD, PhD

    Trial 26-033: RASolute 304: A Phase 3 Multicenter, Open-label, Randomized, 2-Arm Study of Adjuvant Daraxonrasib versus Standard of Care Observation Following Completion of Neoadjuvant and/or Adjuvant Chemotherapy in Patients with Resected Pancreatic Ductal Adenocarcinoma (PDAC)
    Principal Investigator: Brian Wolpin, MD, MPH

    Trial 26-067: RASolute 303: A Phase 3 Global, Multicenter, Open-label, Randomized, 3-Arm Study of Daraxonrasib Monotherapy or Daraxonrasib Plus Gemcitabine and Nab-paclitaxel versus Gemcitabine and Nab-paclitaxel as a First-Line Treatment for Patients with Metastatic Pancreatic Adenocarcinoma
    Principal Investigator: Brian Wolpin, MD, MPH

    Trial 26-215: Phase 1/1b, Multicenter, Open-Label, Study of RMC-5127 in Patients with Advanced KRAS G12V Mutant Solid Tumors Principal Investigator
    Principal Investigator: Alice Shaw, MD, PhD

    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.