A Study of ERAS-601 in People With Chordoma

Inclusion Criteria:

• Age ≥ 18 years.

• Have histologically confirmed chordoma that is not dedifferentiated or poorlydifferentiated subtype.

• Have progressive disease per RECIST 1.1 defined by +20% change between any two scansin the 9 months prior to enrollment.

• Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1

• Recovered from acute, clinically significant toxicities associated withcurrent/recent treatments to acceptable baseline status

• Screening laboratory values must meet the following criteria and should be obtainedwithin 30 days prior to study treatment:

• Absolute neutrophil count (ANC) ≥ 1.5 x 103/m

• Platelet count ≥ 75 × 103/mL without symptomatic bleeding

• Hemoglobin > 9 g/dL

• Serum electrolytes (sodium, potassium, magnesium, phosphorus, calcium) Grade ≤1or within the institutional ranges of normal. If clinically appropriate,electrolytes may be corrected, and values reassessed prior to enrollment.

• AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastases

• Total bilirubin ≤ 1.5 × ULN (except in patients with Gilbert Syndrome who canhave total bilirubin < 3.0 mg/dL)

• Serum creatinine clearance <1.5 times ULN or ≥ 50 mL/min as determined byCockcroft-Gault (Appendix 7) (creatinine clearance need not be calculated ifserum creatinine is within normal limits).

Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to receiving the first dose of study medication.

• Female patients of childbearing potential must be willing to use an adequate methodof contraception, as outlined in the protocol, for the course of the study through 120 days after last dose of study medication.

• Male patients of childbearing potential must agree to use an adequate method ofcontraception, as outlined in the protocol, starting with the first dose of studytherapy through 120 days after the last dose of study therapy.

• Willing to comply with all protocol required- visits, assessments, and procedures.

• Willing to participate in patient interviews for quality-of-life assessment andcomplete patient reported outcomes (PRO) questionnaires

• Non-English speaking patients will not be required to complete patient reportedoutcomes.

Exclusion Criteria:

• Previous treatment with a SHP2 inhibitor.

• Documented PTPN11 mutations.

• Is currently receiving another treatment within 4 weeks of the first dose ofERAS-601 that may impact the outcome of this trial.

• Patients with prior antineoplastic therapy within <21 days or 5 half-lives,whichever is shorter.

• Received radiation within 14 days of Cycle 1, Day 1.

• Received strong inhibitors or inducers of CYP3A4, including grapefruit, grapefruitjuice, and herbal supplements from 7 days prior to the administration of study drug.

• History of calcium and phosphate homeostasis disorder or systemic mineral imbalancewith ectopic soft tissue calcification.

• Gastrointestinal dysfunction that may affect drug absorption.

• Have an untreated, uncontrolled, active infection (bacterial, fungal, or viral)requiring treatment that will impact this protocol.

• History or current evidence of retinal pigment epithelial detachment (RPED), centralserous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED orRVO.

• Sight-limiting degenerative corneal opacity.

• Have any underlying medical condition (e.g. cardiac, pulmonary, hepatic, etc.),psychiatric condition, or social situation that, in the opinion of the Investigator,would compromise patient safety and/or efficacy evaluation as per protocol.

• Incomplete recovery or ongoing complications from prior surgery that in the opinionof the principal investigator will compromise safety of patient and/or efficacyevaluation of protocol.

• Are pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the trial, starting with the screening visit through 120 daysafter the last dose of study therapy.

• Have a second malignancy that is active and in the opinion of the principalinvestigator will compromise safety of patient and/or efficacy evaluation ofprotocol.