First in Human, Dose Escalation Study of AN4005

NCT04999384 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: AN4005X0101AN4005
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 7

Brief Summary

Open-label, multicenter, phase 1 study to investigate the safety, tolerability, and PK of AN4005 in patients with advanced tumors. This study is a first-in-human, dose escalation study with the objective to establish the MTD and/or RP2D of AN4005. Except for Dose Level 0 (50 mg), a traditional "3 + 3 design" will be utilized for dose finding with dose escalation and/or de-escalation as appropriate.

Conditions

Advanced Solid Tumor; Advanced Lymphoma

Outcome Measures

Primary Outcomes (3)

• Number of participants with any adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs, dose interruptions and reductions

  All AEs, SAEs and dose modifications will be collected

  Up to approximately 1 year

• Number of participants with dose limiting toxicities (DLTs)

  An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets the dose-limiting toxicity criteria, unless it can be clearly established that the event is unrelated to treatment

  Up to 28 days

• Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters

  Blood and urine samples will be collected for analysis of lab parameters. Vital signs, physical examinations and organ-specific parameters will be collected at specified time points

  Up to approximately 1 year

Secondary Outcomes (14)

• Maximum observed plasma concentration (Cmax) of AN4005

  Baseline and up to approximately 1 year

• Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of AN4005

  Up to approximately 1 year

• AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of AN4005

  Up to approximately 1 year

• AUC over the dosing interval tau (AUC[0-tau]) of AN4005

  Up to approximately 1 year

• Terminal phase half-life (t1/2) of AN4005

  Up to approximately 1 year

Study Arms (6)

AN4005 dose level 0

ACTIVE COMPARATOR

One sentinel patient will be orally dosed at 50 mg AN4005 BID. If this dose for one cycle is deemed to be tolerable upon review of safety data and PK data, the dose of AN4005 will be escalated to next level: dose level 1.

Drug: AN4005-dose level 0

AN4005 dose level 1

ACTIVE COMPARATOR

Three patients will be orally dosed at 100 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), escalation to dose level 3 (\<1/6 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Drug: AN4005-dose level 1

AN4005 dose level 2

ACTIVE COMPARATOR

Three patients will be orally dosed at 200 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), escalation to dose level 3 (\<1/6 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Drug: AN4005-dose level 2

AN4005 dose level 3

ACTIVE COMPARATOR

Three patients will be orally dosed at 400 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), escalation to dose level 4 (\<1/6 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Drug: AN4005-dose level 3

AN4005 dose level 4

ACTIVE COMPARATOR

Three patients will be orally dosed at 600 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Drug: AN4005-dose level 4

AN4005 food effect

ACTIVE COMPARATOR

The effect of a high-fat meal on the PK of AN4005 will be evaluated in a separate cohort of approximately 6 patients after a safe and clinically relevant dose is identified during the dose finding part of the study.

Drug: AN4005-food effect

Interventions

AN4005-dose level 0 DRUG

50mg BID

AN4005 dose level 0

AN4005-dose level 1 DRUG

100mg BID

AN4005 dose level 1

AN4005-dose level 2 DRUG

200mg BID

AN4005 dose level 2

AN4005-dose level 3 DRUG

400mg BID

AN4005 dose level 3

AN4005-dose level 4 DRUG

600mg BID

AN4005 dose level 4

AN4005-food effect DRUG

Dose to be determined upon the MTD determination

AN4005 food effect

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥ 18 years at the time of informed consent and have provided signed informed consent for the trial.
• \. Willing and able to comply with all aspects of the protocol.
• \. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• \. Life expectancy ≥ 3 months.
• \. Subjects with histologically or cytologically confirmed advanced solid tumors that are metastatic or unresectable, or relapsed or refractory (r/r) lymphoma, and for whom standard life-prolonging measures are not available. Types of lymphoma may include, but are not limited to, natural killer (NK)/T-cell lymphoma, classic Hodgkin lymphoma (cHL), peripheral T-cell lymphoma (PTCL), and diffuse large B-cell lymphoma (DLBCL).
• \. No standard therapy available or standard therapy is considered unsuitable or intolerable according to the Investigator.
• \. Patients with or without measurable disease are considered eligible. Patients who have measurable disease as assessed by the local site investigator and/or radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• \. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. If previously treated with anti-PD-1/PD-L1 therapy, tumor tissue sample obtained following the most recent anti-PD-1/PD-L1 therapy is required. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. For patients with specific types of lymphomas, bone marrow biopsy will be required as appropriate.
• \. Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan.
• \. Patient has organ function as shown by the following:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L.
• Hemoglobin ≥8 g/dL (which may be reached by transfusion).
• Platelets ≥100 x 109/L (which may be reached by transfusion).
• International normalized ratio (INR) ≤1.5.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x upper limit of normal (ULN) or \<5.0 x ULN if liver metastases are present.

You may not qualify if:

• Have been discontinued treatment due to a Grade 3 or higher immune-related AE (irAE) from prior anti-PD-1or anti-PD-L1 therapy, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Have received prior systemic anti-cancer therapy including investigational oncology agents within 4 weeks or 5 half-lives, whichever is shorter.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or returned to baseline. Participants with ≤ Grade 2 neuropathy or alopecia may be eligible.
• At least 6 weeks must have elapsed since CAR-T infusion and subjects must have experienced disease progression, and not have residual circulating CAR-T cells in peripheral blood (based on local assessment). Any encountered treatment-related toxicities must have resolved to Grade ≤1.
• Have received prior palliative radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Uncontrolled tumor-related pain.
• Have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Non live COVID vaccinations or boosters should not occur within 30 days prior to the first dose of study drug and during Cycle 1.
• Are currently participating in a study of an investigational agent or investigational device within 4 weeks or less than 5 half-lives, prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been at least 4 weeks after the last dose of the previous investigational agent (see Number 2 above).
• Have had an allogenic tissue (e.g., bone marrow or stem cells)/solid organ transplant within the past 5 years.
• Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• With a history of another primary malignancy within the past 2 years, with the following exceptions: basal or squamous cell skin cancer, or carcinoma in situ of the cervix or breast that has undergone potentially curative therapy; or patients with a prior history of or clinically stable concurrent malignancy provided the malignancy is clinically insignificant, no treatment is required, and the patient is clinically stable.
• Have known severe hypersensitivity to study treatment components.
• Have an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Have a history of (non-infectious) pneumonitis that has required steroids or have current pneumonitis.

Sponsors & Collaborators

• Adlai Nortye Biopharma Co., Ltd.: lead

Study Sites (7)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Montefiore Einstein Cancer Center

The Bronx, New York, 10461, United States

RECRUITING

Prisma Health Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

RECRUITING

Next Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Study Officials

• Kevin Dryer

  Adlai Nortye USA Inc

  STUDY DIRECTOR

Central Study Contacts

Kirsten Lee

CONTACT

614 362 2760; kirsten.lee@iqvia.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: August 10, 2021
• Study Start: September 27, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CN (3)