A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (FLAGSHP-1)

Erasca

Status and phase: Active, not recruiting; Phase 1

Conditions: Advanced or Metastatic Solid Tumors

Treatments: Drug: Pembrolizumab; Drug: ERAS-601; Drug: Cetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04670679

ERAS-601-01

Details and patient eligibility

About

• To evaluate the safety and tolerability of escalating doses of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies in study participants with advanced or metastatic solid tumors.
• To determine the Maximum Tolerated Dose (MTD) and/or recommended dose (RD) of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
• To characterize the pharmacokinetic (PK) profile of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
• To evaluate the antitumor activity of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.

Full description

This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-601 as a monotherapy and in combination with other cancer therapies. The study will commence with dose escalation of ERAS-601 monotherapy, followed by dose escalation of ERAS-601 in combination with other cancer therapies. Once the monotherapy MTD and/or RD has been determined, then dose expansion of ERAS-601 monotherapy may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations. Once the combination therapy MTD and/or RD has been determined, then dose expansion of that combination may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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
• Able to swallow oral medication
• 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

Exclusion criteria

• Previous treatment with a SHP2 inhibitor
• Documented PTPN11 mutations
• Is currently receiving another study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of ERAS-601
• 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
• Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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200 participants in 5 patient groups

Dose Escalation (Part A): ERAS-601 monotherapy

Experimental group

Description:

ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.

Treatment:

Drug: ERAS-601

Dose Escalation (Part B): ERAS-601 monotherapy

Experimental group

Description:

ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.

Treatment:

Drug: ERAS-601

Dose Escalation (Part C): ERAS-601 monotherapy

Experimental group

Description:

ERAS-601 will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent.

Treatment:

Drug: ERAS-601

Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab

Experimental group

Description:

ERAS-601 will be administered in sequential ascending doses with cetuximab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).

Treatment:

Drug: Cetuximab

Drug: ERAS-601

Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab

Experimental group

Description:

ERAS-601 will be administered in sequential ascending doses with pembrolizumab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).

Treatment:

Drug: ERAS-601

Drug: Pembrolizumab