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

(HERKULES-2 Trial)

Recruiting in Detroit (>99 mi)

+10 other locations

Overseen By Erasca Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Erasca, Inc.

Must not be taking: Anticancer therapies

Disqualifiers: Unstable brain metastases, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two new drugs, ERAS-007 and ERAS-601, in combination with other treatments for advanced lung cancer patients with specific genetic mutations. The goal is to see if these new drugs can enhance the effectiveness of existing treatments by targeting specific pathways in the cancer cells.

Will I have to stop taking my current medications?

The trial requires that you do not take any other systemic anticancer therapy for NSCLC while participating. If you are currently on such treatments, you would need to stop them before joining the trial.

What data supports the effectiveness of the treatment ERAS-007, ERAS-601?

The research on Enhanced Recovery After Surgery (ERAS) programs shows that they can improve patient outcomes by reducing hospital stay length and complications in various surgeries, suggesting that similar principles might support the effectiveness of ERAS-007 and ERAS-601. ^{1 2 3 4 5}

Research Team

Joyce Antal

Principal Investigator

Senior Director, Clinical Development

Eligibility Criteria

Inclusion Criteria

Age ≥ 18 years

Have histologically or cytologically confirmed NSCLC, with presence of EGFR mutation(s) sensitive to EGFR inhibitors, or KRAS G12C mutation

Willing and able to give written informed consent

Exclusion Criteria

You had another type of cancer less than 5 years ago, unless you have been cancer-free for more than 2 years after treatment or if it was an early stage cancer.

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)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ERAS-007 or ERAS-601 is administered in combination with other therapies in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent

3 weeks

Multiple visits (in-person)

Dose Expansion

ERAS-007 or ERAS-601 is administered at the recommended dose in combination with other therapies to evaluate safety and antitumor activity

24 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• ERAS-007
• ERAS-601

Participant Groups

Group I: Dose Expansion (Part 6): ERAS-601 plus sotorasib Experimental Treatment 2 Interventions

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.

Group II: Dose Expansion (Part 5): ERAS-007 plus sotorasib Experimental Treatment 2 Interventions

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.

Group III: Dose Expansion (Part 4): ERAS-007 plus osimertinib Experimental Treatment 2 Interventions

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.

Group IV: Dose Escalation (Part 3): ERAS-601 plus sotorasib Experimental Treatment 2 Interventions

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.

Group V: Dose Escalation (Part 2): ERAS-007 plus sotorasib Experimental Treatment 2 Interventions

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.

Group VI: Dose Escalation (Part 1): ERAS-007 plus osimertinib Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Erasca, Inc.

Lead Sponsor

Trials

8

Recruited

1,200+

Findings from Research

The implementation of Enhanced Recovery After Surgery (ERAS) protocols in pelvic floor reconstructive surgery significantly reduced the length of hospital stay by an average of 16.17 hours and increased the likelihood of patients being discharged within 24 hours post-surgery.

Despite the benefits in recovery time, ERAS protocols did not show differences in operative time, blood loss, complications, or readmission rates compared to standard care, indicating that while ERAS improves recovery, it maintains safety and efficacy similar to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced Recovery Protocols in Urogynecologic and Pelvic Floor Reconstructive Surgery: A Systematic Review and Meta-Analysis. Zacharakis, D., Diakosavvas, M., Prodromidou, A., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Improving Lower Extremity Bypass Patient Outcomes: Enhanced Recovery After Surgery Implementation Project. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Enhanced recovery after surgery for hip fractures: a systematic review and meta-analysis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Association between use of enhanced recovery after surgery protocols and postoperative complications in colorectal surgery in Europe: The EuroPOWER international observational study. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Implementation of enhanced recovery after surgery for pancreatoduodenectomy increases the proportion of patients achieving textbook outcome: A retrospective cohort study. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Enhanced Recovery Protocols in Urogynecologic and Pelvic Floor Reconstructive Surgery: A Systematic Review and Meta-Analysis. [2023]