A First in Human Study of ALX2004 With Advanced or Metastatic Selected Solid Tumors
- Conditions
- NSCLC (Advanced Non-small Cell Lung Cancer)HNSCCCRC (Colorectal Cancer)ESCCColo-rectal CancerHead and Neck CancerEsophageal Squamous Cell Carcinoma (ESCC)
- Interventions
- Drug: ALX2004
- Registration Number
- NCT07085091
- Lead Sponsor
- ALX Oncology Inc.
- Brief Summary
A Phase 1, First in Human, Open-Label Multicenter Study to Evaluate ALX2004, an Antibody Drug Conjugate Targeting EGFR in Participants with Advanced or Metastatic Select Solid Tumors
- Detailed Description
This study consists of Phase 1a Dose finding, comprising of Dose Escalation portion followed by Dose Exploration, and a Phase 1b Dose Expansion. The study will enroll previously treated advanced or metastatic non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), esophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC). Up to 170 patients are expected to be enrolled in the study.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
-
Participants with locally advanced, recurrent or metastatic disease; locally advanced or recurrent disease must not be amenable to resection with curative intent
-
Participants with the following histologically confirmed tumor types for:
-
Dose Escalation:
HNSCC - Received no more than 3 prior lines of therapy in the advanced or metastatic setting NSCLC - For participants with a targetable molecular alteration: received appropriate standard targeted therapy and no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting
For patients without a targetable molecular alteration: received platinum-based chemotherapy and CPI (in combination or separately), and have received no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting
ESCC - Received no more than 3 prior lines of therapy in the advanced/metastatic setting CRC (left-sided) - For participants with a targetable molecular alteration (including dMMR or MSI-H): Received appropriate standard therapy for the alteration, at least 2 prior lines of systemic chemotherapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting For participants without a targetable molecule alteration: Received at least 2 prior lines of systemic chemotherapy (including an oxaliplatin-based chemotherapy), vascular endothelial growth factor (VEGF)-based therapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting.
-
Dose Exploration: All or a subset of tumors tested in Dose Escalation
-
Dose Expansion: Subset of tumors tested in Dose Escalation
-
-
Adequate Bone Marrow Function
-
Adequate Renal & Liver Function
-
Adequate Performance Status
- Participants with disease suitable for local therapy with curative intent.
- Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator
- Prior treatment with any ADCs that have an active TOP1 inhibitor-based component
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ALX2004 Phase 1a (Dose Escalation) ALX2004 ALX2004 will be administered. Patients will be enrolled into escalating dose levels during the dose escalation phase ALX2004 Phase 1a (Dose Exploration) ALX2004 ALX2004 will be administered. All or a subset of tumors tested in dose escalation will enroll into 1 or 2 dose levels during the dose exploration phase ALX2004 Phase 1b (Dose Expansion) ALX2004 ALX2004 will be administered. Patients will receive the recommended phase 2 dose during the dose expansion phase
- Primary Outcome Measures
Name Time Method Phase 1a: Incidence of dose limiting toxicities (DLTs) Up to 28 days Phase 1a: Number and proportion of participants enrolled in the dose escalation phase who experience dose-limiting toxicities (DLTs), received at least one dose of ALX2004 and completed the DLT evaluation
Phase 1a: Incidence of treatment emergent adverse events Up to 2 years from first dose Phase 1a: Adverse Events as characterized by type, frequency, severity (NCI CTCAE v5.0), timing, seriousness, and relationship to the study drug in order to establish the RDE. Laboratory abnormalities as characterized by type, frequency, severity and timing
Phase 1b: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 Up to 2 years from first patient dosed in dose expansion phase Phase 1b: ORR is defined as proportion of participants whose BOR is complete response (CR) or partial response (PR)
- Secondary Outcome Measures
Name Time Method Phase 1a and 1b: Clearance (CL) Up to 2 years To evaluate the clearance of ALX2004
Phase 1a and 1b: Area under the concentration time curve (AUC) Up to 2 years To evaluate the AUC of ALX2004
Phase 1a and 1b: Maximum Concentration (Cmax) Up to 2 years To evaluate the Cmax of ALX2004
Phase 1a and 1b: Time of Maximum Plasma Concentration (Tmax) Up to 2 years To evaluate the Tmax of ALX2004
Phase 1a and 1b: Terminal elimination half-life (t1/2) Up to 2 years To evaluate the t1/2 of ALX2004
Phase 1a and 1b: Progression Free Survival (PFS) Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase PFS is defined as the time (in months) from the date of the first dose of ALX2004 to the date of the first instance of progressive disease or death
Phase 1a and 1b: Overall Survival (OS) Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase OS is defined as the time (in months) from the date of the first dose of ALX2004 to the date of death
Phase 1a and 1b: Best Overall Response (BOR) Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase BOR is defined as the best response reached during the course of the trial from the response categories of CR, PR, SD, PD, and No Response using RECIST v1.1
Phase 1a: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 Up to 2 years from first dose Phase 1a: ORR is defined as proportion of participants whose BOR is complete response (CR) or partial response (PR)
Phase 1a and 1b: DCR (Disease Control Rate) Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase DCR is defined as the proportion of participants whose BOR is PR, CR, or SD
Phase 1a and 1b: Duration of Response (DoR) Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase DoR is defined as the time (in months) from the first instance of a BOR, of CR/PR until the date of the first instance of progressive disease
Phase 1a and 1b: Evaluate the immunogenicity of ALX2004 Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase Measured by the presence of human plasma ADA (Anti-ALX2004 antibodies)
Phase 1b: Incidence of treatment emergent adverse events Up to 2 years from first patient dosed in dose expansion phase AEs as characterized by type, frequency, severity (as graded by the NCI CTCAE v.5.0) timing, seriousness, and relationship to study drug. Laboratory abnormalities as characterized by type, frequency, severity and timing
Trial Locations
- Locations (4)
START Mountain Region
🇺🇸West Valley City, Utah, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
NEXT Oncology
🇺🇸Fairfax, Virginia, United States
Summit Cancer Center
🇺🇸Spokane, Washington, United States
START Mountain Region🇺🇸West Valley City, Utah, United States