ERAS-007 Combination Therapy for Gastrointestinal Cancer

(HERKULES-3 Trial)

Not currently recruiting at 15 trial locations
EC
Overseen ByErasca Clinical Team
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety and effectiveness of a new treatment called ERAS-007, a potential cancer therapy, used with other cancer drugs for advanced gastrointestinal cancers, specifically colorectal cancer (CRC) and pancreatic cancer (PDAC) with certain mutations. The main goal is to determine safe dosage levels and assess how well this combination works against tumors. The trial includes different arms: some participants will receive ERAS-007 with encorafenib and cetuximab, while others will receive it with palbociclib. It seeks individuals with specific genetic mutations in their cancer who are willing to try new treatments and do not have certain other health issues. 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 this new therapy.

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.

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

Research has shown that ERAS-007, when combined with encorafenib and cetuximab, is generally safe and well-tolerated. Studies indicate it works effectively without major safety issues. In patients with a specific type of colorectal cancer (BRAF V600E mutation), the treatment proved to be safe.

For the combination of ERAS-007 with palbociclib, research suggests it is also safe. Most side effects were manageable and reversible. This was observed in patients with certain mutations in colorectal and pancreatic cancers (KRASm/NRASm).

Overall, both combinations have been tested in clinical settings and have demonstrated manageable safety profiles. Most side effects are not severe and can be controlled. These findings suggest that ERAS-007, when combined with other treatments, is generally well-tolerated in patients with advanced gastrointestinal cancers.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about ERAS-007 because it offers a unique approach for treating gastrointestinal cancers, specifically targeting mutations like BRAFm, KRASm, and NRASm. Unlike standard treatments like chemotherapy and targeted therapies such as cetuximab and encorafenib alone, ERAS-007, when combined with these drugs or with palbociclib, aims to enhance effectiveness by targeting multiple pathways simultaneously. This multi-target strategy could potentially improve outcomes for patients with specific gene mutations, offering a novel mechanism of action that may overcome resistance seen with current therapies. Additionally, its oral administration makes it more convenient compared to traditional intravenous treatments.

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

This trial will evaluate ERAS-007 in combination with other drugs for gastrointestinal cancer. Research has shown that ERAS-007, when combined with encorafenib and cetuximab, produced promising results against a specific type of colorectal cancer with a BRAF V600E mutation in both lab and animal studies. This drug combination is already approved for treating this cancer type, which increases confidence in its potential effectiveness. In this trial, some participants will receive ERAS-007 with encorafenib and cetuximab.

Additionally, ERAS-007 combined with palbociclib has demonstrated encouraging early safety results in patients with colorectal or pancreatic cancer that have KRAS or NRAS mutations. Other participants in this trial will receive ERAS-007 with palbociclib. These drug combinations aim to fight tumors by overcoming resistance, a common challenge in cancer treatment. Early findings suggest these combinations might work well, but more research is needed to confirm their effects.12678

Who Is on the Research Team?

JA

Joyce Antal

Principal Investigator

Clinical Development

Are You a Good Fit for This Trial?

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.
See 4 more

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.
See 11 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclibExperimental Treatment2 Interventions
Group II: Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximabExperimental Treatment3 Interventions
Group III: Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclibExperimental Treatment2 Interventions
Group IV: Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximabExperimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Erasca, Inc.

Lead Sponsor

Trials
8
Recruited
1,200+

Published Research Related to This Trial

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.
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]

Citations

Updated results from ERAS-007 plus encorafenib and ...ERAS-007 alone or in combination with encorafenib and cetuximab (EC) showed promising in vitro and in vivo activity in BRAF V600E CRC models, ...
NCT05039177 | A Study of ERAS-007 in Patients With ...This study will serve as a platform study, allowing for evaluation of safety/tolerability and efficacy of ERAS-007 in combination with other cancer therapies.
ERAS-007 plus encorafenib and cetuximab (EC) in ...Preliminary results from ERAS-007 plus encorafenib and cetuximab (EC) in patients (pts) with metastatic BRAF V600E mutated colorectal cancer ( ...
A phase 1b/2 study of agents targeting ...Protect cancer research funding. Tell Congress to ACT NOW to save lives. ASCO Logo · Search · Abstracts · Guidelines · Journal Articles.
5.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39863775/
Encorafenib, cetuximab and chemotherapy in BRAF-mutant ...Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study.
Erasca Provides Update on Clinical Program for ERK ...ERAS-007 100 mg BID-QW + encorafenib + cetuximab (EC) in EC-naïve patients with BRAFm CRC showed a 50% (3/6) response rate (2 cPR, 1 uPR), ...
"Preliminary results from ERAS-007 plus encorafenib and ...... ERAS-007 plus encorafenib and cetuximab ... Conclusions: ERAS-007+EC in pts with BRAF V600E CRC shows acceptable preliminary safety/tolerability ...
Preliminary results from ERAS-007 plus encorafenib and ...Within this study, we are currently evaluating the safety and tolerability of escalating doses of ERAS-007 + EC in pts with BRAF V600E CRC.
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Terms of Service·Privacy Policy·Cookies·Security