A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (FLAGSHP-1)
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| ClinicalTrials.gov Identifier: NCT04670679 |
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Recruitment Status :
Active, not recruiting
First Posted : December 17, 2020
Last Update Posted : November 28, 2023
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Sponsor:
Erasca, Inc.
Information provided by (Responsible Party):
Erasca, Inc.
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Brief Summary:
- To evaluate the safety and tolerability of escalating doses of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies in study participants with advanced or metastatic solid tumors.
- To determine the Maximum Tolerated Dose (MTD) and/or recommended dose (RD) of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
- To characterize the pharmacokinetic (PK) profile of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
- To evaluate the antitumor activity of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced or Metastatic Solid Tumors | Drug: ERAS-601 Drug: Cetuximab Drug: Pembrolizumab | Phase 1 |
This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-601 as a monotherapy and in combination with other cancer therapies. The study will commence with dose escalation of ERAS-601 monotherapy, followed by dose escalation of ERAS-601 in combination with other cancer therapies. Once the monotherapy MTD and/or RD has been determined, then dose expansion of ERAS-601 monotherapy may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations. Once the combination therapy MTD and/or RD has been determined, then dose expansion of that combination may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 200 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-Label, Multi-Center Phase 1/1b Dose Escalation and Expansion Study of ERAS-601 SHP2 Inhibitor as a Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors |
| Actual Study Start Date : | December 15, 2020 |
| Estimated Primary Completion Date : | May 2024 |
| Estimated Study Completion Date : | May 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation (Part A): ERAS-601 monotherapy
ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.
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Drug: ERAS-601
Administered orally |
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Experimental: Dose Escalation (Part B): ERAS-601 monotherapy
ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.
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Drug: ERAS-601
Administered orally |
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Experimental: Dose Escalation (Part C): ERAS-601 monotherapy
ERAS-601 will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent.
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Drug: ERAS-601
Administered orally |
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Experimental: Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab
ERAS-601 will be administered in sequential ascending doses with cetuximab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).
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Drug: ERAS-601
Administered orally Drug: Cetuximab Administered via intravenous infusion
Other Name: Erbitux |
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Experimental: Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab
ERAS-601 will be administered in sequential ascending doses with pembrolizumab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).
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Drug: ERAS-601
Administered orally Drug: Pembrolizumab Administered via intravenous infusion
Other Name: Keytruda |
Primary Outcome Measures :
- Dose Limiting Toxicities (DLT) [ Time Frame: Study Day 1 up to Day 29 ]Based on toxicities observed
- Maximum tolerated dose (MTD) [ Time Frame: Study Day 1 up to Day 29 ]Based on toxicities observed
- Recommended dose (RD) [ Time Frame: Study Day 1 up to Day 29 ]Based on toxicities observed
- Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]Incidence and severity of treatment-emergent AEs and serious AEs
- Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 29 ]Maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)
- Time to achieve Cmax (Tmax) [ Time Frame: Study Day 1 up to Day 29 ]Time to achieve maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)
- Area under the curve [ Time Frame: Study Day 1 up to Day 29 ]Area under the plasma concentration-time curve of ERAS-601 and cetuximab or pembrolizumab (if applicable)
- Half-life [ Time Frame: Study Day 1 up to Day 29 ]Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Secondary Outcome Measures :
- Objective Response Rate (ORR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
- Duration of Response (DOR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
- Time to Response (TTR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
Other Outcome Measures:
- Pharmacodynamic assessment [ Time Frame: Assessed up to 24 months from time of first dose ]Assessment of phosphorylated ERK (pERK) inhibition in PBMCs or tumor tissue by IHC or immunofluorescence.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Willing and able to give written informed consent
- Have histologically or cytologically confirmed advanced or metastatic solid tumor
- There is no available standard systemic therapy available for the patient's tumor histology and/or molecular biomarker profile; or standard therapy is intolerable, not effective, or not accessible; or patient has refused standard therapy
- Able to swallow oral medication
- Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Adequate cardiovascular, hematological, liver, and renal function
- Willing to comply with all protocol-required visits, assessments, and procedures
Exclusion Criteria:
- Previous treatment with a SHP2 inhibitor
- Documented PTPN11 mutations
- Is currently receiving another study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of ERAS-601
- Received prior palliative radiation within 7 days of Cycle 1, Day 1
- Have primary central nervous system (CNS) disease or known active CNS metastases and/or carcinomatous meningitis
- Prior surgery (e.g., gastric bypass surgery, gastrectomy) or gastrointestinal dysfunction (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) that may affect drug absorption
- Active, clinically significant interstitial lung disease or pneumonitis
- History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
- 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
- Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04670679
Locations
| United States, Alabama | |
| University of Alabama at Birmingham | |
| Birmingham, Alabama, United States, 35294 | |
| United States, California | |
| University of California, San Diego | |
| San Diego, California, United States, 92093 | |
| United States, Florida | |
| Sarah Cannon Research Institute (Florida Cancer Specialists) | |
| Sarasota, Florida, United States, 34232 | |
| United States, Massachusetts | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Missouri | |
| Washington University | |
| Saint Louis, Missouri, United States, 63110 | |
| United States, Nevada | |
| Comprehensive Cancer Centers of Nevada | |
| Henderson, Nevada, United States, 89014 | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| United States, North Carolina | |
| University of North Carolina | |
| Chapel Hill, North Carolina, United States, 27599 | |
| United States, Ohio | |
| University of Cincinnati | |
| Cincinnati, Ohio, United States, 45267 | |
| United States, Pennsylvania | |
| University of Pennsylvania | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Tennessee | |
| Sarah Cannon Research Institute (Tennessee Oncology) | |
| Nashville, Tennessee, United States, 37203 | |
| United States, Texas | |
| Mary Crowley Cancer Research | |
| Dallas, Texas, United States, 75251 | |
| The University of Texas MD Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Australia, Victoria | |
| Peter MacCallum Cancer Centre | |
| Melbourne, Victoria, Australia | |
| Australia, Western Australia | |
| Linear Clinical Research | |
| Perth, Western Australia, Australia | |
Sponsors and Collaborators
Erasca, Inc.
Investigators
| Study Director: | Les Brail, PhD | Clinical Development |
| Responsible Party: | Erasca, Inc. |
| ClinicalTrials.gov Identifier: | NCT04670679 |
| Other Study ID Numbers: |
ERAS-601-01 |
| First Posted: | December 17, 2020 Key Record Dates |
| Last Update Posted: | November 28, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Erasca, Inc.:
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SHP2 PTPN11 solid tumor advanced solid tumor metastatic solid tumor neoplasms solid malignancies targeted therapy |
colorectal cancer CRC head and neck squamous cell carcinoma HPV Negative HNSCC molecular alterations cetuximab Erbitux Chordoma |
Additional relevant MeSH terms:
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Neoplasms Pembrolizumab Cetuximab Antineoplastic Agents, Immunological |
Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |