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A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC (HERKULES-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04959981
Recruitment Status : Recruiting
First Posted : July 13, 2021
Last Update Posted : August 8, 2022
Sponsor:
Information provided by (Responsible Party):
Erasca, Inc.

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.

Condition or disease Intervention/treatment Phase
Advanced Non-squamous Non-small-cell Lung Cancer Drug: ERAS-007 Drug: ERAS-601 Drug: Osimertinib Drug: Sotorasib Phase 1 Phase 2

Detailed Description:
This is a Phase 1b/2, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Non-Small-Cell Lung Cancer
Actual Study Start Date : September 2, 2021
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Dose Escalation (Part 1): ERAS-007 plus osimertinib
ERAS-007 will be orally administered in combination with osimertinib to study participants with EGFRm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-007
Administered orally

Drug: Osimertinib
Administered orally
Other Name: Tagrisso

Experimental: Dose Escalation (Part 2): ERAS-007 plus sotorasib
ERAS-007 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-007
Administered orally

Drug: Sotorasib
Administered orally
Other Name: Lumakras

Experimental: Dose Escalation (Part 3): ERAS-601 plus sotorasib
ERAS-601 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-601
Administered orally

Drug: Sotorasib
Administered orally
Other Name: Lumakras

Experimental: Dose Expansion (Part 4): ERAS-007 plus osimertinib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 1) in combination with osimertinib to study participants with EGFRm NSCLC.
Drug: ERAS-007
Administered orally

Drug: Osimertinib
Administered orally
Other Name: Tagrisso

Experimental: Dose Expansion (Part 5): ERAS-007 plus sotorasib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 2) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
Drug: ERAS-007
Administered orally

Drug: Sotorasib
Administered orally
Other Name: Lumakras

Experimental: Dose Expansion (Part 6): ERAS-601 plus sotorasib
ERAS-601 will be orally administered at the recommended dose (as determined from Part 3) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
Drug: ERAS-601
Administered orally

Drug: Sotorasib
Administered orally
Other Name: Lumakras




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLT) [ Time Frame: Study Day 1 up to Day 22 ]
    Based on adverse events observed

  2. Maximum Tolerated Dose (MTD) [ Time Frame: Study Day 1 up to Day 22 ]
    Based on adverse events observed

  3. Recommended Dose (RD) [ Time Frame: Study Day 1 up to Day 22 ]
    Based on adverse events observed

  4. Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]
    Incidence and severity of treatment-emergent AEs and serious AEs


Secondary Outcome Measures :
  1. Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 22 ]
    Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies

  2. Time to achieve Cmax (Tmax) [ Time Frame: Study Day 1 up to Day 22 ]
    Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies

  3. Area under the curve [ Time Frame: Study Day 1 up to Day 22 ]
    Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies

  4. Half-life [ Time Frame: Study Day 1 up to Day 22 ]
    Half-life of ERAS-007 or ERAS-601 and other cancer therapies

  5. Objective Response Rate (ORR) [ Time Frame: Assessed up to 24 months from time of first dose ]
    Based on assessment of radiographic imaging per RECIST version 1.1

  6. Duration of Response (DOR) [ Time Frame: Assessed up to 24 months from time of first dose ]
    Based on assessment of radiographic imaging per RECIST version 1.1



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04959981


Contacts
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Contact: Erasca Clinical Team +1-858-465-6511 clinicaltrials@erasca.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
UC Irvine, Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
UC Los Angeles Recruiting
Santa Monica, California, United States, 90404
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Dana Farber Research Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
United States, New Jersey
Hackensack University Medical Center (John Theurer Cancer Center) Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute (Tennessee Oncology) Recruiting
Nashville, Tennessee, United States, 37203
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Erasca, Inc.
Investigators
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Study Director: Kimberly Komatsubara, M.D. Senior Medical Director
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Responsible Party: Erasca, Inc.
ClinicalTrials.gov Identifier: NCT04959981    
Other Study ID Numbers: ERAS-007-02
First Posted: July 13, 2021    Key Record Dates
Last Update Posted: August 8, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Erasca, Inc.:
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
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action