A First in Human Study of ALX2004 With Advanced or Metastatic Selected Solid Tumors

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

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

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Colo-rectal Cancer; Esophageal Squamous Cell Carcinoma (ESCC); HNSCC; ESCC; NSCLC (Advanced Non-small Cell Lung Cancer); CRC (Colorectal Cancer)
• Intervention / Treatment: Drug: ALX2004; Drug: ALX2004

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.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Athanasios Tsiatis, MD; Phone Number: 650-466-7125; Email: info@alxoncology.com

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • ALX Center 7
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • ALX Center 8
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • ALX Center 3
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • ALX Center 6
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • ALX Center 5
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • ALX Center 4
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • ALX Center 2
  • Washington
    • Spokane, Washington, United States, 99208
      • Recruiting
      • ALX Center 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALX2004 Phase 1a (Dose Escalation); ALX2004 will be administered. Patients will be enrolled into escalating dose levels during the dose escalation phase	Drug: ALX2004; ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV Infusion; Drug: ALX2004; ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV infusion
Experimental: ALX2004 Phase 1a (Dose Exploration); 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	Drug: ALX2004; ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV Infusion; Drug: ALX2004; ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV infusion
Experimental: ALX2004 Phase 1b (Dose Expansion); ALX2004 will be administered. Patients will receive the recommended phase 2 dose during the dose expansion phase	Drug: ALX2004; ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV Infusion; Drug: ALX2004; ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Incidence of dose limiting toxicities (DLTs)	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	Up to 28 days
Phase 1a: Incidence of treatment emergent adverse events	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	Up to 2 years from first dose
Phase 1b: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1	Phase 1b: ORR is defined as proportion of participants whose BOR is complete response (CR) or partial response (PR)	Up to 2 years from first patient dosed in dose expansion phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a and 1b: Maximum Concentration (Cmax)	To evaluate the Cmax of ALX2004	Up to 2 years
Phase 1a and 1b: Time of Maximum Plasma Concentration (Tmax)	To evaluate the Tmax of ALX2004	Up to 2 years
Phase 1a and 1b: Clearance (CL)	To evaluate the clearance of ALX2004	Up to 2 years
Phase 1a and 1b: Area under the concentration time curve (AUC)	To evaluate the AUC of ALX2004	Up to 2 years
Phase 1a and 1b: Terminal elimination half-life (t1/2)	To evaluate the t1/2 of ALX2004	Up to 2 years
Phase 1a: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1	Phase 1a: ORR is defined as proportion of participants whose BOR is complete response (CR) or partial response (PR)	Up to 2 years from first dose
Phase 1a and 1b: Evaluate the immunogenicity of ALX2004	Measured by the presence of human plasma ADA (Anti-ALX2004 antibodies)	Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase
Phase 1b: Incidence of treatment emergent adverse events	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	Up to 2 years from first patient dosed in dose expansion phase
Phase 1a and 1b: Progression Free Survival (PFS)	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: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase
Phase 1a and 1b: Overall Survival (OS)	OS is defined as the time (in months) from the date of the first dose of ALX2004 to the date of death	Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase
Phase 1a and 1b: Best Overall Response (BOR)	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: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase
Phase 1a and 1b: DCR (Disease Control Rate)	DCR is defined as the proportion of participants whose BOR is PR, CR, or SD	Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase
Phase 1a and 1b: Duration of Response (DoR)	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: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase

Collaborators and Investigators

• Sponsor: ALX Oncology Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 27, 2025
• First Submitted That Met QC Criteria: July 23, 2025
• First Posted (Actual): July 25, 2025

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: EGFR; Lung; HNSCC; metastatic; Solid Tumors; Non small cell lung cancer; CRC; Antibody Drug Conjugate; ADC; esophageal; ALX2004; EGFR ADC
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Neoplastic Processes; Esophageal Diseases; Lung Neoplasms; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Colorectal Neoplasms; Colonic Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms
• Other Study ID Numbers: ALX2004-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No