ERAS-007 Combination Therapy for Gastrointestinal Cancer

(HERKULES-3 Trial)

Recruiting at 14 trial locations

Overseen By Erasca Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Erasca, Inc.

Must not be taking: RAS inhibitors

Disqualifiers: Symptomatic brain metastasis, Active infection, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

102 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called ERAS-007 combined with other cancer treatments to see if it is safe and effective for patients with advanced gastrointestinal cancers. The study focuses on patients with specific genetic mutations in their cancer cells, which are often hard to treat. ERAS-007 aims to target these mutations to help stop the cancer from growing.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had anti-cancer therapy within 21 days or 4 half-lives before the first dose of the study drug, whichever is shorter.

What data supports the effectiveness of the drug ERAS-007 for gastrointestinal cancer?

Research shows that combinations including oxaliplatin and capecitabine, which are similar to ERAS-007, have been effective in treating various gastrointestinal cancers, such as colorectal and gastric cancers. ^{1 2 3 4 5}

How is the drug ERAS-007 different from other treatments for gastrointestinal cancer?

ERAS-007 is unique because it is a combination therapy specifically designed for gastrointestinal cancer, potentially offering a novel mechanism of action or treatment approach compared to existing options like capecitabine, oxaliplatin, and irinotecan, which are commonly used in various combinations for similar conditions. ^{1 3 6 7 8}

Research Team

Joyce Antal

Principal Investigator

Clinical Development

Eligibility Criteria

This trial is for adults (18+) with advanced gastrointestinal cancers, specifically metastatic colorectal cancer (CRC) or pancreatic ductal adenocarcinoma (PDAC), that have certain mutations. Participants must be in good health otherwise, able to take oral medication, and willing to follow the study procedures. People with brain metastasis, significant heart disease, recent thrombosis or stroke, prior treatment with similar drugs, or those who are pregnant can't join.

Inclusion Criteria

My organs and bone marrow are working well.

Willing to comply with all protocol-required visits, assessments, and procedures

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have not had major surgery in the last 28 days and do not plan to during the study.

I have a serious lung condition that is not under control.

I have a stomach or intestine condition that affects how I absorb pills.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ERAS-007 is administered in combination with other therapies in sequential ascending doses to determine the Maximum Tolerated Dose (MTD) and Recommended Dose (RD)

4 weeks

Multiple visits (in-person)

Dose Expansion

ERAS-007 is administered at the recommended dose in combination with other therapies to evaluate safety and efficacy

24 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• ERAS-007

Trial Overview The trial tests escalating doses of ERAS-007 combined with other cancer treatments like Encorafenib, Cetuximab, and Palbociclib. It aims to find the safest high dose of ERAS-007 when used together with these therapies and assess how well they work against tumors by measuring their anti-cancer activity.

Participant Groups

Group I: Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclib Experimental Treatment 2 Interventions

ERAS-007 will be orally administered at the recommended dose (as determined from Parts B1a, B2a, B3a or B4a) in combination with palbociclib to study participants with KRASm or NRASm CRC.

Group II: Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab Experimental Treatment 3 Interventions

ERAS-007 will be orally administered at the recommended dose (as determined from Parts A1a, A2a or A3a) in combination with encorafenib and cetuximab to study participants with BRAFm CRC.

Group III: Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclib Experimental Treatment 2 Interventions

ERAS-007 will be orally administered in combination with palbociclib to study participants with KRASm or NRASm CRC and KRASm PDAC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

Group IV: Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab Experimental Treatment 3 Interventions

ERAS-007 will be orally administered in combination with encorafenib and cetuximab to study participants with BRAFm CRC 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

In a phase II study involving 32 patients with previously treated metastatic colorectal cancer, the combination of erlotinib, capecitabine, and oxaliplatin resulted in a 25% partial response rate and 44% of patients achieving stable disease for at least 12 weeks, indicating promising efficacy.

The median progression-free survival was 5.4 months and median overall survival was 14.7 months, with manageable side effects; however, the most common severe toxicities included diarrhea (38%) and nausea (19%), which were reduced by lowering the starting dose of capecitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of capecitabine, oxaliplatin, and erlotinib in previously treated patients with metastastic colorectal cancer. Meyerhardt, JA., Zhu, AX., Enzinger, PC., et al.[2018]

References

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

Phase II study of capecitabine, oxaliplatin, and erlotinib in previously treated patients with metastastic colorectal cancer. [2018]

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

Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabine: a phase II trial. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

Phase I trial of docetaxel, oxaliplatin, and capecitabine (DOC) in untreated gastric cancer patients. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Oxaliplatin and capecitabine chemotherapy for advanced colorectal cancer: a single institution's experience. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Capecitabine, irinotecan, oxaliplatin (CAPIRINOX) and concomitant irradiation in advanced rectal cancer: the Lyon R-02-01 phase I trial. [2018]

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

Combination of oxaliplatin plus irinotecan in patients with gastrointestinal tumors: results of two independent phase I studies with pharmacokinetics. [2018]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

[Irinotecan in combination with 5-fluorouracil and leucovorin in the treatment of metastatic colorectal cancer]. [2013]