A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC

Advanced Non-squamous Non-small-cell Lung Cancer Clinical Trial

— HERKULES-2  

Official title:

A Phase 1b Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Non-Small-Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04959981
• Other study ID #: ERAS-007-02
• Status: Completed
• Phase: Phase 1
• Start date: September 2, 2021
• Est. completion date: April 27, 2023

Study information

• Verified date: July 2023
• Source: Erasca, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

- To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced non-small cell lung cancer (NSCLC). - To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 or ERAS-601 administered in combination with other cancer therapies. - To evaluate the antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies. - To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.

Description:

This is a Phase 1b, open-label, multicenter master protocol evaluating safety, tolerability, and antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced NSCLC. The study will commence with the following dose escalation cohorts: ERAS-007 plus osimertinib in study participants with advanced NSCLC harboring epidermal growth factor receptor-sensitizing mutation(s) (EGFRm); ERAS-007 or ERAS-601 plus sotorasib in study participants with advanced NSCLC harboring Kirsten rat sarcoma G12C mutation (KRAS G12Cm). Dose expansion will follow and will evaluate ERAS-007 or ERAS-601 drug combinations administered at the RD identified from each respective dose escalation cohort in study participants with advanced EGFRm or KRAS G12Cm NSCLC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 27, 2023
• Est. primary completion date: April 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Age = 18 years.
• Willing and able to give written informed consent.
• Have histologically or cytologically confirmed NSCLC, with presence of EGFR mutation(s) sensitive to EGFR inhibitors, or KRAS G12C mutation.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Adequate bone marrow and organ function.
• Have ECOG performance status of 0 or 1.
• Willing to comply with all protocol-required visits, assessments, and procedures.
• Able to swallow oral medication.

Exclusion Criteria:

• Concurrent treatment with any systemic anticancer therapy for NSCLC, including any approved or investigational agent.
• For participants with EGFRm NSCLC: prior therapy with a RAS, RAF, MEK, or ERK inhibitor.
• For participants with KRAS G12Cm NSCLC: prior therapy with a SHP2, ERK, or KRAS G12C inhibitor (depending on which cohort is being considered for enrollment).
• Palliative radiotherapy within 7 days of enrollment.
• History of unacceptable toxicity to treatment with osimertinib or sotorasib.
• Major surgery within the 28 days of enrollment.
• Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at time of enrollment, except for toxicities not considered a safety risk (eg, alopecia, vitiligo, and grade 2 neuropathy due to prior chemotherapy).
• History of another malignancy =5 years prior to first dose, except for patients who are disease-free for >2 years after treatment with curative intent or who have carcinoma in situ.
• Symptomatic and unstable brain metastases, or spinal cord compression, except for patients who have completed definitive therapy (surgery or radiotherapy), are not on steroids, and have a stable neurologic status for a least 2 weeks after completion of the definitive therapy and steroids.
• History of or clinically active ILD, drug induced ILD, or radiation pneumonitis that required steroid treatment.
• Impaired cardiovascular function or clinically significant cardiovascular disease.
• History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO.
• Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study.
• Pregnant or breastfeeding women.
• Contraindication to osimertinib or sotorasib use as per local label.

Related Conditions & MeSH terms

• Advanced Non-squamous Non-small-cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• ERAS-007
Administered orally
• ERAS-601
Administered orally
• Osimertinib
Administered orally
• Sotorasib
Administered orally

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	Dana Farber Research Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Hackensack University Medical Center (John Theurer Cancer Center)	Hackensack	New Jersey
United States	Sarah Cannon Research Institute (Tennessee Oncology)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	UC Irvine, Chao Family Comprehensive Cancer Center	Orange	California
United States	UC Los Angeles	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Erasca, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLT)	Based on adverse events observed	Study Day 1 up to Day 22
Primary	Maximum Tolerated Dose (MTD)	Based on adverse events observed	Study Day 1 up to Day 22
Primary	Recommended Dose (RD)	Based on adverse events observed	Study Day 1 up to Day 22
Primary	Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
Secondary	Plasma concentration (Cmax)	Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies	Study Day 1 up to Day 22
Secondary	Time to achieve Cmax (Tmax)	Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies	Study Day 1 up to Day 22
Secondary	Area under the curve	Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies	Study Day 1 up to Day 22
Secondary	Half-life	Half-life of ERAS-007 or ERAS-601 and other cancer therapies	Study Day 1 up to Day 22
Secondary	Objective Response Rate (ORR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Duration of Response (DOR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose