Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors

NCT04975958 | Completed Phase 1 FDA Drug

• 1 other identifier: AN2025S0101
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open-label, multicenter, Phase 1a study to evaluate the safety, tolerability, PK and preliminary efficacy of AN2025 and AN0025 in double or triple combination treatments with Atezolizumab in patients with locally advanced/metastatic tumors.

Conditions

Locally Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Primary Outcome Measure - Dose Limiting Toxicities (DLTs)

  Number of participants with Dose Limiting Toxicities (DLTs)

  3 weeks

• Primary Outcome Measure - Number of participants with adverse events and serious adverse events

  The safety profile will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

  2 years

Secondary Outcomes (5)

• Overall Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  2 years

• Progression-Free Survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  2 years

• Duration of Response (DOR)

  2 years

• Overall Survival (OS)

  2 years

• Efficacy by Phosphatidylinositol-4,5-bisphosphate 3 Kinase Catalytic Subunit Alpha (PIK3CA) mutation in DLT Observations I and III

  2 years

Study Arms (3)

DLT Observation Period I - AN2025 and Atezolizumab

EXPERIMENTAL

During the DLT Observation I, patients will be treated with AN2025 and Atezolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent. The starting dose of AN2025 is 50 mg. If tolerated, then a subsequent cohort will escalate to 100 mg. A dose de-escalation cohort to 80 mg may occur if the 100 mg is not well tolerated. The dose of Atezolizumab will remain constant at 1200 mg every 3 weeks (Q3W) for each dose level of AN2025 and in each cohort. Atezolizumab is administered intravenously over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

Drug: AN2025; Drug: Atezolizumab 1200 mg in 20 ML Injection

DLT Observation Period II - AN0025 and Atezolizumab

EXPERIMENTAL

During the DLT Observation II, patients will be treated with AN0025 and Atezolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent. The starting dose of AN0025 is 250 mg. If tolerated, then a subsequent cohort will escalate to 500 mg. If 250 mg AN0025 is not tolerated, de-escalate to 125 mg. The dose of Atezolizumab will remain constant at 1200 mg Q3W for each dose level of AN0025 and in each cohort. Atezolizumab is administered intravenously over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

Drug: AN0025; Drug: Atezolizumab 1200 mg in 20 ML Injection

DLT Observation Period III - AN2025, AN0025 and Atezolizumab

EXPERIMENTAL

The DLT Observation III will be started after safety data review by the investigators and the sponsor of the double combination treatments in Observations I and II. Patients enrolled in Observation III will start with the recommended dose of AN0025 from Observation II, 1200 mg Atezolizumab, and AN2025 will start from 50 mg QD. Patients will be treated with all three study drugs until the patient experiences disease progression, unacceptable toxicity or withdraws consent. The dose of Atezolizumab will be the same (i.e., 1200 mg Q3W) regardless of dose levels of AN2025 and cohorts. Atezolizumab is administered intravenously over 60 minutes every three weeks. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes. The dose of AN0025 as determined in Observation II will remain constant for each dose level of AN2025 and each cohort, unless the investigators and the sponsor determine that the toxicity comes from the AN0025 + Atezolizumab combination.

Drug: AN2025; Drug: AN0025; Drug: Atezolizumab 1200 mg in 20 ML Injection

Interventions

AN2025 DRUG

oral administration

Also known as: BKM120

DLT Observation Period I - AN2025 and Atezolizumab; DLT Observation Period III - AN2025, AN0025 and Atezolizumab

AN0025 DRUG

oral administration

Also known as: E7046

DLT Observation Period II - AN0025 and Atezolizumab; DLT Observation Period III - AN2025, AN0025 and Atezolizumab

Atezolizumab 1200 mg in 20 ML Injection DRUG

infusion

Also known as: Tecentriq

DLT Observation Period I - AN2025 and Atezolizumab; DLT Observation Period II - AN0025 and Atezolizumab; DLT Observation Period III - AN2025, AN0025 and Atezolizumab

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.
• Diagnosed with histologically confirmed locally advanced and nonresectable, or metastatic disease.
• Have received at least one line of prior systemic therapy or no alternative therapy to prolong survival exists.
• Have received no more than 4 prior lines of systemic therapy for advanced disease. Prior therapy in an adjuvant or neoadjuvant setting is not considered as a prior line of systemic therapy.
• Have measurable disease per RECIST 1.1 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.
• 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 ≥9 g/dL (which may be reached by transfusion 2 weeks prior to the start of the study treatment).
• Platelets ≥100 x 109/L (which may be reached by transfusion).
• International normalized ratio (INR) ≤1.5.

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, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Have received prior systemic anti-cancer therapy including investigational 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.
• 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.
• Severe, 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 during Cycle 1 or within 30 days prior to the first dose of study drug.
• Are currently participating in a study of an investigational agent or have used an investigational device within 4 weeks 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/solid organ transplant.
• 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 exception of basal or squamous cell skin cancer, or carcinoma in situ of the cervix or breast that has undergone potentially curative therapy.
• Have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• 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 required steroids or have current pneumonitis.
• Have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis.

Sponsors & Collaborators

• Adlai Nortye Biopharma Co., Ltd.: lead

Study Sites (5)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists - Lake Mary Cancer Center

Lake Mary, Florida, 32746, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

NYU Grossman School of Medicine

New York, New York, 10016, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Interventions

NVP-BKM120; E7046; atezolizumab; Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Robert Atkinson, PhD, MSCR

  Adlai Nortye US Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: July 26, 2021
• Study Start: September 7, 2021
• Primary Completion: January 24, 2025
• Study Completion: January 24, 2025
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)