MC# 21-07

• 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

Part D2 HNSCC HPV Negative

• Histologically or pathologically (cytologically) confirmed HPV-negative recurrent/metastatic HNSCC
• Prior therapy for HNSCC
  • At least 1 systemic regimen in the recurrent/metastatic setting
    • Systemic therapy administered with curative intent does NOT count as a line of therapy in the recurrent/metastatic setting if recurrence occurs >6 months from the last dose of the regimen. Accordingly, if recurrence occurs ≤6 months from the last dose of the regimen, then it DOES count as a line of prior therapy in the recurrent/metastatic setting.
  • Must include a platinum-based chemotherapy
  • Must include an immune checkpoint inhibitor-based regimen. The immune checkpoint inhibitor regimen could be the same as the platinum-based regimen.
  • No prior anti-EGFR therapy, eg, cetuximab

• 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

Part D2 HNSCC HPV Negative

• Patients who received prior cetuximab or anti-EGFR therapy