MC# 21-07 - An Open-Label, Multi-Center Phase I/Ib Dose Escalation and Expansion Study of ERAS-601 SHP2 Inhibitor as a Monotherapy and in Combination with Other Anti-Cancer Therapies in Patients with Advanced or Metastatic Solid Tumors

  • Agent(s): ERAS-601
  • Disease Type(s): Colorectal, Solid Tumor, Squamous Cell Carcinoma of Head and Neck
  • Phase(s): I
  • Drug Classification(s): Small Molecule, Targeted Therapy
  • Molecular Target(s): MAPK, SHP2

Mechanism of Action

ERAS-601 targets SHP2, a protein that plays an important role in modulating normal cell growth, and disrupts MAPK signaling, thereby shutting down the ability of cancer cells to grow and proliferate.

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of ERAS-601
  • Determine the recommended dose of ERAS-601 alone and in combination with MEK inhibitor
  • How proteins that indicate the status of your disease are affected with use of ERAS-601
  • If ERAS-601, alone or in combination with a MEK inhibitor, prevents or delays tumor growth or shrinks existing tumors
  • How much of ERAS-601 is absorbed into the blood and how fast it is removed
  • If research tests can be used in the future to predict who will benefit from ERAS-601
Inclusion Criteria
  • Age ≥ 18 years
  • Willing and able to give written informed consent
  • Have histologically or cytologically confirmed advanced or metastatic solid tumor
  • There is no available standard systemic therapy available for the patient's tumor histology and/or molecular biomarker profile; or standard therapy is intolerable, not effective, or not accessible; or patient has refused standard therapy
  • Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  • Adequate cardiovascular, hematological, liver, and renal function
  • Willing to comply with all protocol-required visits, assessments, and procedures

Additional Inclusion Criteria per Cohorts

Part A, B, C1, D1, and C2

  • There is no available standard systemic therapy available for the patient’s tumor histology and/or molecular biomarker profile; or standard therapy is intolerable, not effective, or not accessible; or patient has refused standard therapy.
  • Part C2, D2 Archival tumor tissue or tumor tissue obtained from a biopsy at screening must be available and submitted (sample may be submitted after enrollment). Note: Tissue submission is optional for dose-escalation cohorts, but highly encouraged.

Part C2

  • All patients enrolled in Part C2 must have a documented NF1 mutation, a BRAF Class III mutation, and/or a diagnosis of low-grade serous ovarian cancer or GIST

Part D2 HNSCC HPV Negative

  • Histologically or pathologically (cytologically) confirmed HPV-negative HNSCC
  • Prior therapy for HNSCC
    • At least 1 and no more than 2 systemic regimens
    • Must include a platinum-based chemotherapy
    • Must include an immune checkpoint inhibitor either in combination with a platinum-based regimen or separately
    • No prior anti-EGFR therapy, eg, cetuximab

Part D2 CRC wtRAS and wtBRAF

  • Histologically or cytologically confirmed KRAS wild-type, NRAS wild-type, and BRAF wild-type CRC
  • Prior therapy for metastatic CRC
    • Must include at least one fluoropyrimidine-based regimen that contains oxaliplatin and/or irinotecan
    • Must have received prior EGFR-inhibitor treatment
    • Prior treatment with regorafenib or TAS-102 (trifluridine and tipiracil) is not allowed
    • Patients with known microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) CRC must receive prior immune checkpoint inhibitor, pembrolizumab or nivolumab, if indicated per local practice, unless contraindicated
Exclusion Criteria
  • Previous treatment with a SHP2 inhibitor
  • Documented PTPN11 mutations
  • Is currently receiving another study therapy or has participated in a study of aninvestigational agent and received study therapy within 4 weeks of the first dose of ERAS-601
  • Patients with prior antineoplastic therapy within <21 days or 5 half-lives, whichever is shorter
  • Received prior palliative radiation within 7 days of Cycle 1, Day 1
  • Have primary central nervous system (CNS) disease or known active CNS metastases and/or carcinomatous meningitis
  • Prior surgery (e.g., gastric bypass surgery, gastrectomy) or gastrointestinal dysfunction (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) that may affect drug absorption
  • Active, clinically significant interstitial lung disease or pneumonitis
  • History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
  • Have any underlying medical condition, psychiatric condition, or social situation that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs
  • Have a planned major surgery, or incomplete recovery from any prior surgery prior to the start of study therapy
  • Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
  • Have a history of additional invasive metastatic disease except for the following:
    • Individuals with a history of invasive metastatic disease are eligible if they have been disease-free for at least 2 years and are deemed by the Investigator to be at low risk for recurrence of that metastatic disease
    • Individuals with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or local papillary thyroid cancer, who have undergone therapy with curative intent

Additional Exclusion Criteria per Cohorts

Part D2 HNSCC HPV Negative

  • Patients who received prior cetuximab or anti-EGFR therapy

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04670679

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Re: MC# 21-07