ERAS-007 + ERAS-601 for Advanced Cancer

(HERKULES-1 Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment that combines two experimental drugs, ERAS-007 and ERAS-601, to determine their safety and effectiveness in shrinking tumors. Researchers aim to identify the optimal dose and schedule for these drugs in individuals with advanced or metastatic solid tumors, particularly those with specific molecular changes. Individuals with these types of tumors and no other effective treatment options may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that ERAS-007 is generally safe for patients. In earlier studies, only 14.9% of patients stopped treatment due to side effects, and no deaths were linked to the treatment. This suggests that ERAS-007 is safe when used alone.

For the combination of ERAS-007 and ERAS-601, early results also suggest safety. These findings offer promise for prospective trial participants. Although the trial is still in the early stages and determining the optimal dose, the current data provide reassurance about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ERAS-007 and ERAS-601 for advanced cancer because they target unique molecular alterations in tumors, which might not be addressed by standard options like chemotherapy, radiation, or surgery. Unlike traditional treatments that often affect both healthy and cancerous cells, ERAS-007 and ERAS-601 are designed to specifically target cancer cells with particular molecular markers, potentially reducing side effects. Additionally, the combination approach of ERAS-007 with ERAS-601 offers a novel strategy that could enhance the effectiveness of treatment by attacking the cancer from multiple angles. This targeted approach is promising because it could lead to better outcomes and a more personalized treatment plan for patients with advanced or metastatic solid tumors.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that ERAS-007 yields positive results for advanced cancer. One study found that 23% of patients with certain non-colorectal solid tumors responded to the treatment. For those with specific BRAF-driven tumors, the response rate increased to 44%. In this trial, some participants will receive ERAS-007 as monotherapy, while others will receive a combination of ERAS-007 with another treatment, ERAS-601, to determine if it enhances effectiveness against different solid tumors. Although more research is needed, these early findings suggest that ERAS-007, both alone and combined with ERAS-601, could be a promising option for treating advanced cancers. ^{1 3 5 6 7}

Who Is on the Research Team?

Wei Lin, M.D.

Principal Investigator

Chief Medical Officer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04866134

NCT04866134 | A Study of ERAS-007 as Monotherapy or ... To evaluate the safety and tolerability of ERAS-007 monotherapy administered once weekly (QW) and twice daily-once weekly (BID-QW).

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11522

A phase 1 study of ERAS-601 as a monotherapy ... The median time on combination treatment was 5.06 months, with 8 out of 9 pts remaining on the study. Conclusions: The most common toxicities ...

3. investors.erasca.com investors.erasca.com/news-releases/news-release-details/erasca-presents-promising-preliminary-phase-11b-monotherapy-data

News Release Details HERKULES-1 is a Phase 1b/2 clinical trial that will include evaluation of ERAS-601 in combination with ERAS-007 in advanced solid tumors.

4. clinicaltrial.be clinicaltrial.be/en/details/44528?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

A Study of ERAS-007 as Monotherapy or in Combination ... The dose escalation phases of this study will test ERAS-007 monotherapy administered BID-QW as a monotherapy or in combination with ERAS-601 in ...

5. withpower.com withpower.com/trial/phase-2-neoplasms-4-2021-e52c4

ERAS-007 + ERAS-601 for Advanced Cancer ... Trial Overview The trial is testing ERAS-007 alone with different dosing schedules and in combination with ERAS-601 for safety, tolerability, ideal dosage, ...

6. clinicaltrial.be clinicaltrial.be/en/details/44528?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_eligible=0&only_active=0

A Study of ERAS-007 as Monotherapy or in Combination ... The dose escalation phases of this study will test ERAS-007 monotherapy administered BID-QW as a monotherapy or in combination with ERAS-601 in ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04866134/

Clinical Trial: NCT04866134 To evaluate the safety and tolerability of ERAS-007 monotherapy administered once weekly (QW) and twice daily-once weekly (BID-QW).