Clinical trial NCT04959981: A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Non-squamous Non-small-cell Lung Cancer
Keywords: EGFR
epidermal growth factor receptor
mutation
biomarker
NSCLC
Tagrisso
osimertinib
ERK
MAPK
sotorasib
Lumakras
KRAS
G12C
SHP2
PTPN11
molecular alterations
Kirsten rat sarcoma
Non-small cell lung cancer
Lung neoplasms
Thoracic neoplasms
ERAS-601
ERAS-007
Lead sponsor: Erasca, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: Study Day 1 up to Day 22
measure: Maximum Tolerated Dose (MTD)
timeFrame: Study Day 1 up to Day 22
measure: Recommended Dose (RD)
timeFrame: Study Day 1 up to Day 22
measure: Adverse Events
timeFrame: Assessed up to 24 months from time of first dose
Secondary outcomes:
measure: Plasma concentration (Cmax)
timeFrame: Study Day 1 up to Day 22
measure: Time to achieve Cmax (Tmax)
timeFrame: Study Day 1 up to Day 22
measure: Area under the curve
timeFrame: Study Day 1 up to Day 22
measure: Half-life
timeFrame: Study Day 1 up to Day 22
measure: Objective Response Rate (ORR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Duration of Response (DOR)
timeFrame: Assessed up to 24 months from time of first dose
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Orange
country: United States
facility: UC Irvine, Chao Family Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UC Los Angeles
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Research Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center (John Theurer Cancer Center)
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (Tennessee Oncology)
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: Senior Director, Clinical Development
name: Joyce Antal
role: STUDY_DIRECTOR
References: