ERAS-007 + ERAS-601 for Advanced Cancer

(HERKULES-1 Trial)

Recruiting at 4 trial locations

Overseen By Erasca Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Erasca, Inc.

Must not be taking: ERK inhibitors, SHP2 inhibitors, MAPK inhibitors

Disqualifiers: Pregnancy, Breastfeeding, Gastrointestinal dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

Trial Summary

What is the purpose of this trial?

* To evaluate the safety and tolerability of ERAS-007 monotherapy administered once weekly (QW) and twice daily-once weekly (BID-QW). * To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 monotherapy administered BID-QW. * To characterize the pharmacokinetic (PK) profile of ERAS-007 monotherapy. * To determine the optimal dose and schedule of ERAS-007 monotherapy. * To evaluate antitumor activity of ERAS-007 in various solid tumors. * To evaluate the safety and tolerability of ERAS-007 (BID-QW) and ERAS-601 (twice daily for three weeks on and 1 week off (BID 3/1)) when administered in combination. * To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 administered in combination with ERAS-601. * To characterize the pharmacokinetic (PK) profile of ERAS-007 and ERAS-601 when administered in combination. * To evaluate antitumor activity of ERAS-007 and ERAS-601 when administered in combination in various solid tumors * To evaluate antitumor activity of ERAS-007 and ERAS-601 when administered in combination in various solid tumors

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have received certain treatments recently, like other study therapies or specific cancer treatments. It's best to discuss your current medications with the trial team.

What safety data exists for ERAS-007 and ERAS-601 in humans?

The research articles provided do not contain specific safety data for ERAS-007 or ERAS-601. However, a meta-analysis of molecular target anticancer drugs, which may include similar types of treatments, found an increased risk of serious and fatal adverse events compared to placebo. This suggests that while these drugs can be effective, they may also carry significant risks. ^{1 2 3 4 5}

Research Team

Wei Lin, M.D.

Principal Investigator

Chief Medical Officer

Eligibility Criteria

Adults over 18 with advanced or metastatic solid tumors and specific molecular alterations, who have no standard treatment options left or can't tolerate them. They must be able to take oral meds, have recovered from previous treatments' side effects, and have a life expectancy of more than 12 weeks.

Inclusion Criteria

I am mostly active and doctors expect me to live more than 12 weeks.

I have recovered from side effects of my previous cancer treatments.

My advanced cancer has a specific genetic change.

Exclusion Criteria

Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.

I have been treated with an ERK inhibitor before.

Have any underlying medical condition, psychiatric condition, or social situation that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ERAS-007 monotherapy administered BID-QW in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent

Up to 24 months

Weekly visits

Dose Expansion

ERAS-007 monotherapy administered at 250 mg QW to participants with specific molecular alterations

Up to 24 months

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ERAS-007
• ERAS-601

Trial Overview The trial is testing ERAS-007 alone with different dosing schedules and in combination with ERAS-601 for safety, tolerability, ideal dosage, pharmacokinetics (how the body processes the drugs), and effectiveness against various solid tumors.

Participant Groups

Group I: Dose Expansion (Part C): ERAS-007 Monotherapy, BID-QW dosing (if necessary) Experimental Treatment 1 Intervention

Depending on data generated from Part A, ERAS-007 monotherapy may be administered at the BID-QW RD to participants with advanced or metastatic solid tumors that harbor specific molecular alterations.

Group II: Dose Expansion (Part B): ERAS-007 Monotherapy, QW dosing Experimental Treatment 1 Intervention

ERAS-007 monotherapy will be administered at 250 mg QW to participants with advanced or metastatic solid tumors that harbor specific molecular alterations.

Group III: Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601 Experimental Treatment 2 Interventions

Experimental: Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601 ERAS-007 will be administered BID-QW in combination with ERAS-601 administered BID 3/1 to study participants with advanced or metastatic solid tumors that harbor specific molecular targets in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

Group IV: Dose Escalation (Part A): ERAS-007 Monotherapy, BID-QW dosing Experimental Treatment 1 Intervention

ERAS-007 monotherapy will be administered BID-QW in sequential ascending doses to participants with advanced or metastatic solid tumors 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 combination of osimertinib and platinum-based chemotherapy (OPP) demonstrated a high objective response rate of 90.9% in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer, indicating strong efficacy.

The treatment was well-tolerated, with no treatment-related deaths and an acceptable safety profile, as only 14.9% of patients discontinued due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: The OPAL Study. Saito, R., Sugawara, S., Ko, R., et al.[2023]

In a study of 45 patients with advanced non-small-cell lung cancer (NSCLC) who had received multiple prior chemotherapy regimens, S-1 showed a disease control rate of 62.2%, with 8.9% of patients achieving a partial response.

S-1 was well tolerated with manageable side effects, as no grade 4 toxicities were observed, but the overall response rate was considered insufficient for effective treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of S-1 as third-line or further chemotherapy in patients with advanced non-small-cell lung cancer. Miyoshi, S., Ito, R., Katayama, H., et al.[2021]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of S-1, a novel oral fluoropyrimidine, and biweekly administration of docetaxel for previously treated advanced non-small-cell lung cancer. [2021]

2. Greece pubmed.ncbi.nlm.nih.gov

S-1 combined with oxaliplatin as first line chemotherapy for Chinese advanced gastric cancer patients. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: The OPAL Study. [2023]

4. Japan pubmed.ncbi.nlm.nih.gov

Phase II trial of S-1 as third-line or further chemotherapy in patients with advanced non-small-cell lung cancer. [2021]

5. India pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. [2020]