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

Official title

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

Overview

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

• 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
• Drug ALX2004
  ALX2004 is a novel ADC targeting EGFR. Drug: ALX2004 IV infusion

Primary outcome measures

• Phase 1a: Incidence of dose limiting toxicities (DLTs) [Time frame: Up to 28 days]
• Phase 1a: Incidence of treatment emergent adverse events [Time frame: Up to 2 years from first dose]
• Phase 1b: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 [Time frame: Up to 2 years from first patient dosed in dose expansion phase]

Secondary outcome measures (12)

• Phase 1a and 1b: Maximum Concentration (Cmax) [Time frame: Up to 2 years]
• Phase 1a and 1b: Time of Maximum Plasma Concentration (Tmax) [Time frame: Up to 2 years]
• Phase 1a and 1b: Clearance (CL) [Time frame: Up to 2 years]
• Phase 1a and 1b: Area under the concentration time curve (AUC) [Time frame: Up to 2 years]
• Phase 1a and 1b: Terminal elimination half-life (t1/2) [Time frame: Up to 2 years]
• Phase 1a: Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 [Time frame: Up to 2 years from first dose]
• Phase 1a and 1b: Evaluate the immunogenicity of ALX2004 [Time frame: 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 [Time frame: Up to 2 years from first patient dosed in dose expansion phase]
• Phase 1a and 1b: Progression Free Survival (PFS) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: Phase 1a: Up to 2 years from first dose. Phase 1b: Up to 2 years from first patient dosed in dose expansion phase]

Eligibility criteria

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

• 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.
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• ALX Center 7 — Tampa
• ALX Center 8 — Farmington Hills
• ALX Center 3 — Grand Rapids
• ALX Center 6 — Portland
• ALX Center 5 — Houston
• ALX Center 4 — West Valley City
• ALX Center 2 — Fairfax
• ALX Center 1 — Spokane

Identifiers

NCT: NCT07085091 · ALX2004-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗