AN0025 and Pembrolizumab Combination in Advanced Solid Tumors

NCT04432857 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: AN0025S01032019-003960-37KEYNOTE-879MK-3475-879
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 6

Brief Summary

This is an open-label, multicenter, phase Ib study to evaluate the safety and preliminary efficacy of AN0025 in combination with pembrolizumab in patients with locally advanced/metastatic tumors. It will include a dose-limiting toxicity observation phase followed by an expansion phase. All enrolled patients will be treated with AN0025 and Pembrolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent, or for a maximum of 35 cycles (approximately 2 years). The dose of pembrolizumab will remain constant at 200 mg every 3 weeks (Q3W) for each dose level of AN0025 and in each cohort.

Conditions

Triple-negative Breast Cancer; NSCLC, Squamous or Non-Squamous; Urothelial Carcinoma of the Bladder; Microsatellite Stable (MSS) Colorectal Cancer (CRC); Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure

  Number of participants with Dose Limiting Toxicities (DLTs)

  3 weeks

Secondary Outcomes (4)

• ORR and 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 PD-L1 expression

  2 years

Study Arms (6)

Ph1a: Urothelial carcinoma of the bladder and NSCLC

EXPERIMENTAL

Patients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.

Drug: AN0025; Drug: Pembrolizumab

Phase 1b: Urothelial carcinoma of the bladder

EXPERIMENTAL

Patients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.

Drug: AN0025; Drug: Pembrolizumab

Phase 1b: Non-Small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

Patients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.

Drug: AN0025; Drug: Pembrolizumab

Phase 1b: Triple-negative breast cancer (TNBC)

EXPERIMENTAL

Patients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.

Drug: AN0025; Drug: Pembrolizumab

Phase 1b: Cervical

EXPERIMENTAL

Patients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.

Drug: AN0025; Drug: Pembrolizumab

Phase 1b: Microsatellite Stable (MSS) Colorectal Cancer (CRC)

EXPERIMENTAL

Patients will receive AN0025 orally once daily (QD); Pembrolizumab, 200mg as an intravenous infusion over 30 minutes every 3 weeks.

Drug: AN0025; Drug: Pembrolizumab

Interventions

AN0025 DRUG

oral administration

Also known as: E7046

Ph1a: Urothelial carcinoma of the bladder and NSCLC; Phase 1b: Cervical; Phase 1b: Microsatellite Stable (MSS) Colorectal Cancer (CRC); Phase 1b: Non-Small Cell Lung Cancer (NSCLC); Phase 1b: Triple-negative breast cancer (TNBC); Phase 1b: Urothelial carcinoma of the bladder

Pembrolizumab DRUG

Infusion

Also known as: KEYTRUDA®, MK-3475-879

Ph1a: Urothelial carcinoma of the bladder and NSCLC; Phase 1b: Cervical; Phase 1b: Microsatellite Stable (MSS) Colorectal Cancer (CRC); Phase 1b: Non-Small Cell Lung Cancer (NSCLC); Phase 1b: Triple-negative breast cancer (TNBC); Phase 1b: Urothelial carcinoma of the bladder

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.
• 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.
• Patients diagnosed with one of the following tumor types:
• A. Urothelial carcinoma of the bladder B. NSCLC, Squamous or Non-Squamous C. TNBC D. Cervical cancer E. MSS CRC
• Have progressed on treatment with an anti-PD-1/PD-L1monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (cohort A, B or C) and have failed available standard of care treatment or deemed inappropriate candidates for additional standard treatments by the investigator. PD-1 treatment progression is defined by meeting all of the following criteria:
• For cohort A, B and C:
• Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb.
• Has demonstrated disease progression after PD-1/PD-L1 as defined by RECIST v1.1. The initial evidence of disease progression (PD) is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression. i,ii
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• i. Seymour et al; iRECIST: Guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 18: e143-52 ii. This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.
• For cohort B (NSCLC):
• Prior treatments must include an anti-PD-1/PD-L1 mAb AND a platinum-based chemotherapy.
• Must include anti-PD-1/PD-L1 mAb or platinum-based chemotherapy was used in one of the following settings:

You may not qualify if:

• Have been discontinued treatment due to a Grade 3 or higher immune-related (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 prior to treatment.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or returned to baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Have received prior 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-CNS disease.
• 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 or have participated 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.
• 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 to 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.
• Participants with inflammatory bowel disease.
• Have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis.

Sponsors & Collaborators

• Adlai Nortye Biopharma Co., Ltd.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah School of Medicine Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Richmond, Virginia, 22908, United States

Location

Centre Léon Bérard

Lyon, France

Location

Gustave Roussy

Paris, 94805, France

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Spinocerebellar Degenerations; Colorectal Neoplasms; Uterine Cervical Neoplasms

Interventions

E7046; pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Robert Atkinson, Ph.D.

  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: June 11, 2020
• First Posted: June 16, 2020
• Study Start: August 20, 2020
• Primary Completion: May 31, 2024
• Study Completion: January 30, 2025
• Last Updated: June 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); US (4)