Testing ERAS-601 for treating chordoma

A Phase 1b/2 Study of ERAS-601 SHP2 Inhibitor as a Monotherapy in Patients With Advanced and Progressing Chordoma

This study is testing a new drug called ERAS-601 to see if it can safely help adults with advanced chordoma feel better and manage their condition.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT06957327 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of ERAS-601, a SHP2 inhibitor, in patients with advanced and progressing chordoma. Participants must be at least 18 years old and have confirmed chordoma that is not dedifferentiated or poorly differentiated. The study aims to determine if ERAS-601 can provide a treatment option with minimal side effects for this challenging condition. Patients will be monitored for disease progression and treatment response according to established criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed chordoma that is not dedifferentiated or poorly differentiated and has shown progressive disease.

Not a fit: Patients with dedifferentiated or poorly differentiated chordoma may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced chordoma, potentially improving their outcomes.

How similar studies have performed: While this approach is novel for chordoma, similar studies with SHP2 inhibitors have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years.
* Have histologically confirmed chordoma that is not dedifferentiated or poorly differentiated subtype.
* Have progressive disease per RECIST 1.1 defined by +20% change between any two scans in 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 with current/recent treatments to acceptable baseline status
* Screening laboratory values must meet the following criteria and should be obtained within 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 ≤1 or 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 can have total bilirubin \< 3.0 mg/dL)
  * Serum creatinine clearance \<1.5 times ULN or ≥ 50 mL/min as determined by Cockcroft-Gault (Appendix 7) (creatinine clearance need not be calculated if serum 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 method of 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 of contraception, as outlined in the protocol, starting with the first dose of study therapy 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 and complete patient reported outcomes (PRO) questionnaires

Exclusion Criteria:

* Previous treatment with a SHP2 inhibitor.
* Documented PTPN11 mutations.
* Is currently receiving another treatment within 4 weeks of the first dose of ERAS-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, grapefruit juice, and herbal supplements from 7 days prior to the administration of study drug.
* History of calcium and phosphate homeostasis disorder or systemic mineral imbalance with 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), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO.
* 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 opinion of the principal investigator will compromise safety of patient and/or efficacy evaluation of protocol.
* Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study therapy.
* Have a second malignancy that is active and in the opinion of the principal investigator will compromise safety of patient and/or efficacy evaluation of protocol.

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center - Suffolk (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (Recruiting)

Study contacts

• Principal investigator: Mrinal Gounder, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Mrinal Gounder, MD

Conditions Chordoma; Advanced and Progressing Chordoma; ERAS-601 SHP2 Inhibitor; 25-071