Acute Myeloid LeukemiaPhase 1/2HERKULES-4NCT05279859
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Hematologic Malignancies
A Phase 1/2 study testing ERAS-007, ERAS-601 and Gilteritinib in people with Acute Myeloid Leukemia, run by Erasca, Inc. at 4 sites in United States.
Trial summary
To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- ERAS-007, ERAS-601 and Gilteritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 4 sitesUnited States
- Study dates
- 15 Mar 2022to 1 Jun 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Willing and able to give written informed consent.
- Diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization classification.
- Relapsed after or refractory to first-line AML therapy.
- Positive for FLT3 mutation in bone marrow or whole blood.
- Eastern Cooperative Oncology Group performance status ≤ 2 with no deterioration during screening period.
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- Adequate hepatic and renal function.
- Recovery from non-hematologic AEs associated with prior therapy to baseline CTCAE v5 Grade 0 or 1, except for AEs not considered a safety risk (eg, alopecia or vitiligo).
- Able to take oral medication with no medical conditions that prevent swallowing and absorbing oral medications.
- Willing to comply with all protocol-required visits, assessments, and procedures.
Who cannot join
- Diagnosis of AML secondary to prior chemotherapy or other neoplasms (except for MDS).
- Diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia (chronic myeologenous leukemia in blast crisis).
- Clinically active central nervous system leukemia.
- Second or later hematologic relapse or prior salvage therapy for refractory disease.
- For participants being considered for ERAS-007+gilteritinib treatment: prior therapy with ERK inhibitor.
- For participants being considered for ERAS-601+gilteritinib treatment: prior therapy with SHP2 inhibitor.
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- Anticancer therapy ≤14 days prior to first dose (except hydroxyurea given for controlling blast count), or ≤5 half-lives prior to first dose, whichever is shorter.
- Palliative radiation ≤7 days prior to first dose.
- Major surgery within 28 days of enrollment.
- Contraindication to gilteritinib use as per local label.
- Known hypersensitivity to any of the components of ERAS-007 or ERAS-601.
- Clinically active infection, requiring systemic therapy.
- Impaired cardiovascular function or clinically significant cardiovascular disease.
- History of thromboembolic or cerebrovascular events ≤6 months prior to first dose.
- History of other malignancy ≤3 years prior to first dose.
- History of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or risk factors to RPED or RVO.
- History of or clinically active interstitial lung disease (ILD), drug induced ILD, or radiation pneumonitis that required steroid treatment.
- Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the participant inappropriate to participate in the study.
- Pregnant or breastfeeding women.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Texas Oncology
Dallas, Texas, 75251
NEXT Oncology Virginia
Fairfax, Virginia, 22031
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase 1b/2 Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Hematologic Malignancies
- To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies.
- To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 or ERAS-601 administered in combination with other cancer therapies.
- To evaluate the preliminary efficacy of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies.
- To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.
Read the detailed description
This is a Phase 1b/2, open-label, multicenter master protocol evaluating safety, tolerability, and preliminary efficacy of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies. The study will commence with dose escalation cohorts (ERAS-007 plus gilteritinib and ERAS-601 plus gilteritinib) in study participants with relapsed or refractory (R/R) Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia (AML). Dose expansion will follow and will evaluate ERAS-007 or ERAS-601 drug combinations administered at the RD identified from each respective dose escalation cohort in study participants with R/R FLT-3 mutated AML.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- ERAS-007, ERAS-601, Gilteritinib
- Keywords
- AML, FLT3, mutation, relapsed, refractory, gilteritinib, Xospata, MAPK, SHP2, ERK
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ERAS-007Drug
Administered orally
ERAS-601Drug
Administered orally
GilteritinibDrug
Also called Xospata
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (Part 1): ERAS-007 plus gilteritinib | Experimental | ERAS-007 will be administered in combination with gilteritinib to study participants with R/R FLT3 mutated AML in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent. Receives: Drug: ERAS-007; Drug: Gilteritinib |
| Dose Escalation (Part 2): ERAS-601 plus gilteritinib | Experimental | ERAS-601 will be administered in combination with gilteritinib to study participants with R/R FLT3 mutated AML in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent. Receives: Drug: ERAS-601; Drug: Gilteritinib |
| Dose Expansion (Part 3): ERAS-007 plus gilteritinib | Experimental | ERAS-007 will be administered at the recommended dose (as determined from Part 1) in combination with gilteritinib to study participants with R/R FLT3 mutated AML. Receives: Drug: ERAS-007; Drug: Gilteritinib |
| Dose Expansion (Part 4): ERAS-601 plus gilteritinib | Experimental | ERAS-601 will be administered at the recommended dose (as determined from Part 2) in combination with gilteritinib to study participants with R/R FLT3 mutated AML. Receives: Drug: ERAS-601; Drug: Gilteritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicities (DLT)
Based on adverse events observed during dose escalation
Measured: Study Day 1 up to Day 29
Maximum Tolerated Dose (MTD)
Based on adverse events observed during dose escalation
Measured: Study Day 1 up to Day 29
Recommended Dose (RD)
Based on adverse events observed during dose escalation
Measured: Study Day 1 up to Day 29
Adverse Events
Incidence and severity of treatment-emergent AEs and serious AEs
Measured: Assessed up to 24 months from time of first dose
Secondary outcomes (7)
Plasma concentration (Cmax)
Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 29
Time to achieve Cmax (Tmax)
Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 29
Area under the curve
Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 29
Half-life
Half-life of ERAS-007 or ERAS-601 and other cancer therapies
Measured: Study Day 1 up to Day 29
Antileukemic activity
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh); CR rate
Measured: Assessed up to 24 months from time of first dose
Duration of antileukemic activity
Duration of CR/CRh (DOCR/DOCRh)
Measured: Assessed up to 24 months from time of first dose
Duration of antileukemic activity
Duration of CR (DOCR)
Measured: Assessed up to 24 months from time of first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start15 Mar 2022 (estimated)
- Primary completion1 Mar 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Why it stopped: Sponsor decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasca, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Les Brail, Ph.D., Study director, Medical Monitor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05279859
- Sponsor's protocol ID
- ERAS-007-04
- Acronym
- HERKULES-4
- Status last verified
- Jun 2022
- First submitted
- 5 Mar 2022
- Last updated
- 15 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT05279859
- Acronym / sponsor ID
- HERKULES-4 / ERAS-007-04
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML, FLT3, mutation, relapsed, refractory, gilteritinib, Xospata, MAPK
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Erasca, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Mar 2022 (estimated)
- Primary completion
- 1 Mar 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies.
- To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 or ERAS-601 administered in combination with other cancer therapies.
- To evaluate the preliminary efficacy of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies.
- To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.
Detailed description
This is a Phase 1b/2, open-label, multicenter master protocol evaluating safety, tolerability, and preliminary efficacy of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies. The study will commence with dose escalation cohorts (ERAS-007 plus gilteritinib and ERAS-601 plus gilteritinib) in study participants with relapsed or refractory (R/R) Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia (AML). Dose expansion will follow and will evaluate ERAS-007 or ERAS-601 drug combinations administered at the RD identified from each respective dose escalation cohort in study participants with R/R FLT-3 mutated AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation (Part 1): ERAS-007 plus gilteritinib | Experimental | Drug: ERAS-007, Drug: GilteritinibERAS-007 will be administered in combination with gilteritinib to study participants with R/R FLT3 mutated AML in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent. |
| Dose Escalation (Part 2): ERAS-601 plus gilteritinib | Experimental | Drug: ERAS-601, Drug: GilteritinibERAS-601 will be administered in combination with gilteritinib to study participants with R/R FLT3 mutated AML in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent. |
| Dose Expansion (Part 3): ERAS-007 plus gilteritinib | Experimental | Drug: ERAS-007, Drug: GilteritinibERAS-007 will be administered at the recommended dose (as determined from Part 1) in combination with gilteritinib to study participants with R/R FLT3 mutated AML. |
| Dose Expansion (Part 4): ERAS-601 plus gilteritinib | Experimental | Drug: ERAS-601, Drug: GilteritinibERAS-601 will be administered at the recommended dose (as determined from Part 2) in combination with gilteritinib to study participants with R/R FLT3 mutated AML. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 18 years.
- Willing and able to give written informed consent.
- Diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization classification.
- Relapsed after or refractory to first-line AML therapy.
- Positive for FLT3 mutation in bone marrow or whole blood.
Key exclusion criteria (19 listed)
- Diagnosis of AML secondary to prior chemotherapy or other neoplasms (except for MDS).
- Diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia (chronic myeologenous leukemia in blast crisis).
- Clinically active central nervous system leukemia.
- Second or later hematologic relapse or prior salvage therapy for refractory disease.
- For participants being considered for ERAS-007+gilteritinib treatment: prior therapy with ERK inhibitor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ERAS-007Administered orally | Drug | Dose Escalation (Part 1): ERAS-007 plus gilteritinib, Dose Expansion (Part 3): ERAS-007 plus gilteritinib |
| ERAS-601Administered orally | Drug | Dose Escalation (Part 2): ERAS-601 plus gilteritinib, Dose Expansion (Part 4): ERAS-601 plus gilteritinib |
| GilteritinibAlso: XospataAdministered orally | Drug | Dose Escalation (Part 1): ERAS-007 plus gilteritinib, Dose Escalation (Part 2): ERAS-601 plus gilteritinib, Dose Expansion (Part 3): ERAS-007 plus gilteritinib, Dose Expansion (Part 4): ERAS-601 plus gilteritinib |
Primary outcome
Dose Limiting Toxicities (DLT)
Time frame: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
Maximum Tolerated Dose (MTD)
Time frame: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
Recommended Dose (RD)
Time frame: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
Adverse Events
Time frame: Assessed up to 24 months from time of first dose
Incidence and severity of treatment-emergent AEs and serious AEs
7 secondary outcomes
Plasma concentration (Cmax)
Time frame: Study Day 1 up to Day 29
Time to achieve Cmax (Tmax)
Time frame: Study Day 1 up to Day 29
Area under the curve
Time frame: Study Day 1 up to Day 29
Half-life
Time frame: Study Day 1 up to Day 29
Antileukemic activity
Time frame: Assessed up to 24 months from time of first dose
Duration of antileukemic activity
Time frame: Assessed up to 24 months from time of first dose
Duration of antileukemic activity
Time frame: Assessed up to 24 months from time of first dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Les Brail, Ph.D. study director
Medical Monitor
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ERAS-007, ERAS-601 and Gilteritinib in people with Acute Myeloid Leukemia, run by Erasca, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicities (DLT) (time frame: Study Day 1 up to Day 29). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2022.