Colo-rectal Cancer, CRC (Colorectal Cancer), ESCC, Esophageal Squamous Cell Carcinoma (ESCC), Head and Neck Cancer, HNSCC, NSCLC (Advanced Non-small Cell Lung Cancer)
Conditions
Keywords
ALX2004, EGFR, Solid Tumors, metastatic, Antibody Drug Conjugate, ADC, HNSCC, CRC, Lung, Non small cell lung cancer, esophageal, EGFR ADC
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.
Interventions
DRUGALX2004
ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV Infusion
Sponsors
ALX Oncology Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The dose escalation and dose exploration portions of the study will be non-randomized. For each tumor type selected for dose expansion, either one or two dose(s) and schedule(s) may be tested. If two doses/schedules are tested, allocation will be randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with locally advanced, recurrent or metastatic histologically confirmed HNSCC, NSCLC, ESCC, CRC; locally advanced or recurrent disease must not be amenable to resection with curative intent 1. Dose Escalation: Participants who have relapsed or progressed following prior anticancer therapy in the advanced/metastatic setting and for whom no approved or standard therapy is available. 2. Dose Exploration and Dose Expansion: The following tumor-specific criteria also apply. These cohorts will include all or a subset of these tumors. 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 participants 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 - 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. * Adequate Bone Marrow Function * Adequate Renal \& Liver Function * Adequate Performance Status
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: Terminal elimination half-life (t1/2) | Up to 2 years | To evaluate the t1/2 of ALX2004 |
| 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: 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 |
| 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 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 |
Countries
United States
Contacts
CONTACTAthanasios Tsiatis, MD
Outcome results
None listed