Advanced Non-squamous Non-small-cell Lung CancerPhase 1HERKULES-2NCT04959981
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC
A Phase 1 study testing ERAS-007, ERAS-601 and Osimertinib in people with Advanced Non-squamous Non-small-cell Lung Cancer, run by Erasca, Inc. at 11 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Advanced Non-squamous Non-small-cell Lung Cancer
- What is being tested?
- ERAS-007, ERAS-601 and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 11 sitesUnited States
- Study dates
- 2 Sep 2021to 27 Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Research Institute
Boston, Massachusetts, 02215
Henry Ford Health System
Detroit, Michigan, 48202
City of Hope
Duarte, California, 91010
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Hackensack University Medical Center (John Theurer Cancer Center)
Hackensack, New Jersey, 07601
Sarah Cannon Research Institute (Tennessee Oncology)
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
UC Irvine, Chao Family Comprehensive Cancer Center
Orange, California, 92868
UC Los Angeles
Santa Monica, California, 90404
About this study
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
- 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.
Read the 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.
- Being tested
- ERAS-007, ERAS-601, Osimertinib, Sotorasib
- 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
- Medical subject headings
- Noonan Syndrome, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Thoracic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ERAS-007Drug
Administered orally
ERAS-601Drug
Administered orally
OsimertinibDrug
Also called Tagrisso
Administered orally
SotorasibDrug
Also called Lumakras
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (Part 1): ERAS-007 plus osimertinib | Experimental | 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. Receives: Drug: ERAS-007; Drug: Osimertinib |
| Dose Escalation (Part 2): ERAS-007 plus sotorasib | Experimental | 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. Receives: Drug: ERAS-007; Drug: Sotorasib |
| Dose Escalation (Part 3): ERAS-601 plus sotorasib | Experimental | 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. Receives: Drug: ERAS-601; Drug: Sotorasib |
| Dose Expansion (Part 4): ERAS-007 plus osimertinib | Experimental | 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. Receives: Drug: ERAS-007; Drug: Osimertinib |
| Dose Expansion (Part 5): ERAS-007 plus sotorasib | Experimental | 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. Receives: Drug: ERAS-007; Drug: Sotorasib |
| Dose Expansion (Part 6): ERAS-601 plus sotorasib | Experimental | 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. Receives: Drug: ERAS-601; Drug: Sotorasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicities (DLT)
Based on adverse events observed
Measured: Study Day 1 up to Day 22
Maximum Tolerated Dose (MTD)
Based on adverse events observed
Measured: Study Day 1 up to Day 22
Recommended Dose (RD)
Based on adverse events observed
Measured: Study Day 1 up to Day 22
Adverse Events
Incidence and severity of treatment-emergent AEs and serious AEs
Measured: Assessed up to 24 months from time of first dose
Secondary outcomes (6)
Plasma concentration (Cmax)
Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 22
Time to achieve Cmax (Tmax)
Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 22
Area under the curve
Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 22
Half-life
Half-life of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 22
Objective Response Rate (ORR)
Based on assessment of radiographic imaging per RECIST version 1.1
Measured: Assessed up to 24 months from time of first dose
Duration of Response (DOR)
Based on assessment of radiographic imaging per RECIST version 1.1
Measured: Assessed up to 24 months from time of first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2021
- Study start2 Sep 2021
- Primary completion27 Apr 2023
- Study completion27 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Non-squamous Non-small-cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasca, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joyce Antal, Study director, Senior Director, Clinical Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04959981
- Sponsor's protocol ID
- ERAS-007-02
- Acronym
- HERKULES-2
- Status last verified
- Jul 2023
- First submitted
- 2 Jul 2021
- Last updated
- 25 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04959981
- Acronym / sponsor ID
- HERKULES-2 / ERAS-007-02
- Keywords
- EGFR, epidermal growth factor receptor, mutation, biomarker, NSCLC, Tagrisso, osimertinib, ERK
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Erasca, Inc.Industry (pharma, biotech, devices)
- Study start
- 2 Sep 2021 (actual)
- Primary completion
- 27 Apr 2023 (actual)
- Study completion
- 27 Apr 2023 (actual)
- First posted
- 13 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation (Part 1): ERAS-007 plus osimertinib | Experimental | Drug: ERAS-007, Drug: OsimertinibERAS-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. |
| Dose Escalation (Part 2): ERAS-007 plus sotorasib | Experimental | Drug: ERAS-007, Drug: SotorasibERAS-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. |
| Dose Escalation (Part 3): ERAS-601 plus sotorasib | Experimental | Drug: ERAS-601, Drug: SotorasibERAS-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. |
| Dose Expansion (Part 4): ERAS-007 plus osimertinib | Experimental | Drug: ERAS-007, Drug: OsimertinibERAS-007 will be orally administered at the recommended dose (as determined from Part 1) in combination with osimertinib to study participants with EGFRm NSCLC. |
| Dose Expansion (Part 5): ERAS-007 plus sotorasib | Experimental | Drug: ERAS-007, Drug: SotorasibERAS-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. |
| Dose Expansion (Part 6): ERAS-601 plus sotorasib | Experimental | Drug: ERAS-601, Drug: SotorasibERAS-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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ERAS-007Administered orally | Drug | Dose Escalation (Part 1): ERAS-007 plus osimertinib, Dose Escalation (Part 2): ERAS-007 plus sotorasib, Dose Expansion (Part 4): ERAS-007 plus osimertinib, Dose Expansion (Part 5): ERAS-007 plus sotorasib |
| ERAS-601Administered orally | Drug | Dose Escalation (Part 3): ERAS-601 plus sotorasib, Dose Expansion (Part 6): ERAS-601 plus sotorasib |
| OsimertinibAlso: TagrissoAdministered orally | Drug | Dose Escalation (Part 1): ERAS-007 plus osimertinib, Dose Expansion (Part 4): ERAS-007 plus osimertinib |
| SotorasibAlso: LumakrasAdministered orally | Drug | Dose Escalation (Part 2): ERAS-007 plus sotorasib, Dose Escalation (Part 3): ERAS-601 plus sotorasib, Dose Expansion (Part 5): ERAS-007 plus sotorasib, Dose Expansion (Part 6): ERAS-601 plus sotorasib |
Primary outcome
Dose Limiting Toxicities (DLT)
Time frame: Study Day 1 up to Day 22
Based on adverse events observed
Maximum Tolerated Dose (MTD)
Time frame: Study Day 1 up to Day 22
Based on adverse events observed
Recommended Dose (RD)
Time frame: Study Day 1 up to Day 22
Based on adverse events observed
Adverse Events
Time frame: Assessed up to 24 months from time of first dose
Incidence and severity of treatment-emergent AEs and serious AEs
6 secondary outcomes
Plasma concentration (Cmax)
Time frame: Study Day 1 up to Day 22
Time to achieve Cmax (Tmax)
Time frame: Study Day 1 up to Day 22
Area under the curve
Time frame: Study Day 1 up to Day 22
Half-life
Time frame: Study Day 1 up to Day 22
Objective Response Rate (ORR)
Time frame: Assessed up to 24 months from time of first dose
Duration of Response (DOR)
Time frame: Assessed up to 24 months from time of first dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joyce Antal study director
Senior Director, Clinical Development
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ERAS-007, ERAS-601 and Osimertinib in people with Advanced Non-squamous Non-small-cell Lung Cancer, run by Erasca, Inc. at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicities (DLT) (time frame: Study Day 1 up to Day 22). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2023.