Ignite Creation Date:
2025-12-24 @ 2:39 PM
Ignite Modification Date:
2025-12-25 @ 4:28 PM
Study NCT ID:
NCT05279859
Status:
WITHDRAWN
Last Update Posted:
2022-06-15
First Post:
2022-03-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Hematologic Malignancies
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015470', 'term': 'Leukemia, Myeloid, Acute'}, {'id': 'D012008', 'term': 'Recurrence'}], 'ancestors': [{'id': 'D007951', 'term': 'Leukemia, Myeloid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000609080', 'term': 'gilteritinib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Sponsor decision.', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2022-03-15', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-06', 'completionDateStruct': {'date': '2025-06-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-06-13', 'studyFirstSubmitDate': '2022-03-05', 'studyFirstSubmitQcDate': '2022-03-14', 'lastUpdatePostDateStruct': {'date': '2022-06-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-03-15', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-03-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Dose Limiting Toxicities (DLT)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Based on adverse events observed during dose escalation'}, {'measure': 'Maximum Tolerated Dose (MTD)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Based on adverse events observed during dose escalation'}, {'measure': 'Recommended Dose (RD)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Based on adverse events observed during dose escalation'}, {'measure': 'Adverse Events', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Incidence and severity of treatment-emergent AEs and serious AEs'}], 'secondaryOutcomes': [{'measure': 'Plasma concentration (Cmax)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies'}, {'measure': 'Time to achieve Cmax (Tmax)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies'}, {'measure': 'Area under the curve', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies'}, {'measure': 'Half-life', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Half-life of ERAS-007 or ERAS-601 and other cancer therapies'}, {'measure': 'Antileukemic activity', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh); CR rate'}, {'measure': 'Duration of antileukemic activity', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Duration of CR/CRh (DOCR/DOCRh)'}, {'measure': 'Duration of antileukemic activity', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Duration of CR (DOCR)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['AML', 'FLT3', 'mutation', 'relapsed', 'refractory', 'gilteritinib', 'Xospata', 'MAPK', 'SHP2', 'ERK'], 'conditions': ['Acute Myeloid Leukemia']}, 'descriptionModule': {'briefSummary': '* 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.\n* 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.\n* To evaluate the preliminary efficacy of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies.\n* To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Willing and able to give written informed consent.\n* Diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization classification.\n* Relapsed after or refractory to first-line AML therapy.\n* Positive for FLT3 mutation in bone marrow or whole blood.\n* Eastern Cooperative Oncology Group performance status ≤ 2 with no deterioration during screening period.\n* Adequate hepatic and renal function.\n* 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).\n* Able to take oral medication with no medical conditions that prevent swallowing and absorbing oral medications.\n* Willing to comply with all protocol-required visits, assessments, and procedures.\n\nExclusion Criteria:\n\n* Diagnosis of AML secondary to prior chemotherapy or other neoplasms (except for MDS).\n* Diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia (chronic myeologenous leukemia in blast crisis).\n* Clinically active central nervous system leukemia.\n* Second or later hematologic relapse or prior salvage therapy for refractory disease.\n* For participants being considered for ERAS-007+gilteritinib treatment: prior therapy with ERK inhibitor.\n* For participants being considered for ERAS-601+gilteritinib treatment: prior therapy with SHP2 inhibitor.\n* 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.\n* Palliative radiation ≤7 days prior to first dose.\n* Major surgery within 28 days of enrollment.\n* Contraindication to gilteritinib use as per local label.\n* Known hypersensitivity to any of the components of ERAS-007 or ERAS-601.\n* Clinically active infection, requiring systemic therapy.\n* Impaired cardiovascular function or clinically significant cardiovascular disease.\n* History of thromboembolic or cerebrovascular events ≤6 months prior to first dose.\n* History of other malignancy ≤3 years prior to first dose.\n* History of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or risk factors to RPED or RVO.\n* History of or clinically active interstitial lung disease (ILD), drug induced ILD, or radiation pneumonitis that required steroid treatment.\n* 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.\n* Pregnant or breastfeeding women.'}, 'identificationModule': {'nctId': 'NCT05279859', 'acronym': 'HERKULES-4', 'briefTitle': 'A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Hematologic Malignancies', 'organization': {'class': 'INDUSTRY', 'fullName': 'Erasca, Inc.'}, 'officialTitle': 'A Phase 1b/2 Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Hematologic Malignancies', 'orgStudyIdInfo': {'id': 'ERAS-007-04'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dose Escalation (Part 1): ERAS-007 plus gilteritinib', 'description': '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.', 'interventionNames': ['Drug: ERAS-007', 'Drug: Gilteritinib']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Escalation (Part 2): ERAS-601 plus gilteritinib', 'description': '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.', 'interventionNames': ['Drug: ERAS-601', 'Drug: Gilteritinib']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Expansion (Part 3): ERAS-007 plus gilteritinib', 'description': '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.', 'interventionNames': ['Drug: ERAS-007', 'Drug: Gilteritinib']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Expansion (Part 4): ERAS-601 plus gilteritinib', 'description': '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.', 'interventionNames': ['Drug: ERAS-601', 'Drug: Gilteritinib']}], 'interventions': [{'name': 'ERAS-007', 'type': 'DRUG', 'description': 'Administered orally', 'armGroupLabels': ['Dose Escalation (Part 1): ERAS-007 plus gilteritinib', 'Dose Expansion (Part 3): ERAS-007 plus gilteritinib']}, {'name': 'ERAS-601', 'type': 'DRUG', 'description': 'Administered orally', 'armGroupLabels': ['Dose Escalation (Part 2): ERAS-601 plus gilteritinib', 'Dose Expansion (Part 4): ERAS-601 plus gilteritinib']}, {'name': 'Gilteritinib', 'type': 'DRUG', 'otherNames': ['Xospata'], 'description': 'Administered orally', 'armGroupLabels': ['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']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '75251', 'city': 'Dallas', 'state': 'Texas', 'country': 'United States', 'facility': 'Texas Oncology', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas MD Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '22031', 'city': 'Fairfax', 'state': 'Virginia', 'country': 'United States', 'facility': 'NEXT Oncology Virginia', 'geoPoint': {'lat': 38.84622, 'lon': -77.30637}}], 'overallOfficials': [{'name': 'Les Brail, Ph.D.', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Medical Monitor'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Erasca, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}