ERAS-007 + ERAS-601 for Non-Small Cell Lung Cancer

(HERKULES-2 Trial)

No longer recruiting at 10 trial 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for advanced non-small cell lung cancer (NSCLC) to evaluate their safety and effectiveness when combined with other cancer drugs. Researchers aim to determine the best dose of two experimental drugs, ERAS-007 and ERAS-601, by combining them with existing treatments like osimertinib or sotorasib. The trial is open to individuals with NSCLC who have specific gene changes (EGFR or KRAS G12C mutations) that make them suitable for these drug combinations. Participants should have been living with NSCLC and not have received certain prior treatments.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new drugs.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining osimertinib with other targeted treatments is safe and feasible. This suggests that using ERAS-007 with osimertinib might also be well-tolerated. Studies indicate that sotorasib is safe for patients with advanced lung cancer in real-world settings, implying that combining it with ERAS-007 could also be manageable for patients.

For ERAS-601 with sotorasib, research has shown that sotorasib is safe and effective in similar patient groups. These findings suggest that combining it with ERAS-601 might also be safe.

Since this trial is in the early stages, it primarily focuses on understanding safety and determining the right doses. Safety data is still being collected, but early studies are promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they target the MAPK pathway, a key player in cell growth and division that is often overactive in non-small cell lung cancer (NSCLC). Unlike standard treatments that might not specifically target this pathway, ERAS-007 and ERAS-601 are designed to inhibit proteins in the MAPK pathway, potentially stopping cancer growth more effectively. Additionally, these treatments are combined with osimertinib and sotorasib, which are already known to target specific mutations like EGFR and KRAS G12C, respectively. This combination approach could offer a more tailored and potent attack on the cancer cells.

What evidence suggests that this trial's treatments could be effective for advanced non-small cell lung cancer?

This trial will evaluate different treatment combinations for specific types of lung cancer. One arm will study ERAS-007 combined with osimertinib for patients with EGFR-mutated NSCLC. Studies have shown that combining osimertinib with other targeted treatments can be safe and may offer benefits. Research suggests that ERAS-007, when paired with osimertinib, targets changes in the MAPK pathway, which plays a role in cell growth and cancer development.

Another arm will investigate ERAS-007 combined with sotorasib, while a separate arm will study ERAS-601 combined with sotorasib, both focusing on KRAS G12C mutations common in some lung cancers. Sotorasib has proven effective in real-world settings for advanced lung cancer with these mutations. These treatment combinations aim to improve outcomes by targeting specific genetic changes in cancer cells. ^{1 2 3 4 6}

Who Is on the Research Team?

Joyce Antal

Principal Investigator

Senior Director, Clinical Development

Are You a Good Fit for This Trial?

Inclusion Criteria

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

Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ERAS-007
• ERAS-601

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39724403

evaluating osimertinib combination with targeted therapies ... Conclusions: Combinations of osimertinib with other targeted therapies appeared to be feasible and safe and may offer clinical benefit to ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730425000075

CNS Outcomes of Osimertinib Plus Chemotherapy in ... Conclusion. Continuation of osimertinib and chemotherapy beyond disease progression on osimertinib reduced the risk of CNS progression in patients with EGFR ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04959981

A Study of Anti-Cancer Therapies Targeting the MAPK ... 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.

4. lungcancerjournal.info lungcancerjournal.info/article/S0169-5002(25)00441-6/fulltext

EGFR mutation testing across the osimertinib clinical program We report post-hoc analyses of pooled EGFR mutation tissue testing across osimertinib clinical trials, highlighting testing challenges and supporting best ...

5. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(21)00282-X/pdf

Overcoming Osimertinib Resistance in Advanced Non- ... Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer. Nat Commun 2017;8:14768. https ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40320171/

Overall Survival in EGFR-Mutant Advanced NSCLC ... Despite advances in tyrosine kinase inhibitor treatments, long-term survival of patients with advanced EGFRm NSCLC remains poor.