ALG.APV-527 First-in-human Study

NCT05934539 | Unknown Phase 1 FDA Drug

• 1 other identifier: ALG.APV-527-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

A first-in-human, multicenter, open-label, dose escalation and dose expansion phase 1 study in patients with advanced solid tumors to evaluate the safety of intravenously administered ALG.APV-527 (Short title: ALG.APV-527 first-in-human study). Adult patients with advanced/metastatic solid tumors likely to express 5T4 antigen who have failed standard of care regimens for their cancer, have become refractory to standard treatment, or for whom no effective therapy exists based on investigator judgment may be enrolled in this study. Part 1 (Dose Escalation): Approximately 36 evaluable patients planned to be enrolled. Part 2 (Dose Expansion): Approximately 20 evaluable patients planned to be enrolled.

Conditions

Solid Tumor

Keywords

Solid Tumor; 5T4

Outcome Measures

Primary Outcomes (2)

• Number of participants with dose-limiting toxicities (DLTs)

  Number of participants with DLTs during the 28 days following the first administration of Q2W ALG.APV 527 or during the 42 days following Q3W ALG.APV 527

  28 days for Q2W

• Overall Response Rate

  The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence based on the response evaluation criteria in solid tumors (RECIST), v1.1

  Through completion of Expansion Phase. Approximately 24 months.

Secondary Outcomes (2)

• Pharmacokinetic measure- Peak Plasma Concentration (Cmax)

  Through completion of both Dose Escalation and Dose Expansion ( Approx 42 months)

• Pharmacokinetic measure- Area under the plasma concentration versus time curve (AUC)

  Through completion of both Dose Escalation and Dose Expansion ( Approx 42 months)

Study Arms (1)

ALG.APV-527

EXPERIMENTAL

Part 1 Dose Escalation using ALG.APV-527 doses with a starting dose of 0.1 mg/kg and projected 6 dose cohorts will be explored to determine the MTD and/or the RP2D. Part 1 consists of a 3 + 3 dose-escalation examination of ALG.APV-527 single agent therapy in adult patients with RECIST Version1.1-measurable advanced solid tumors. Part 2 Dose Expansion with ALG.APV-527 based on RP2D determined during Dose Escalation.

Drug: ALG.APV-527

Interventions

ALG.APV-527 DRUG

ALG.APV-527 is a human bispecific antibody in the ADAPTIR™ format with a silenced immunoglobulin 1 (IgG1) Fc domain targeting the co-stimulatory receptor 4-1BB, expressed on immune cells such as CD8+ T cells and natural killer (NK) cells, and the tumor associated antigen 5T4. ALG.APV-527 is being co-developed by Alligator Bioscience AB (Lund, Sweden) and Aptevo Therapeutics Inc. (Seattle, WA, USA) as a cancer immunotherapy.

Also known as: No other intervention names are planned for this study

ALG.APV-527

Eligibility Criteria

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

You may qualify if:

• Have provided signed informed consent form (ICF) for participation in the study.
• Have a diagnosis of advanced solid tumor malignancy (histologically or cytologically documented) that is metastatic or unresectable, have received standard of care therapy, and remaining therapeutic options are participation in a clinical study or non-curative therapy including best supportive care.
• Have one of the following tumors: non-small cell lung cancer (NSCLC), gastric/gastro-esophageal cancer, head and neck squamous cell carcinoma, renal cell cancer, ovarian cancer, breast cancer, malignant pleural mesothelioma, cervical cancer, colorectal cancer, urothelial carcinoma, endometrial cancer, pancreatic cancer, or prostate cancer.
• Must be ≥ 18 years of age.
• ECOG performance status 0-1.
• Has provided tumor tissue biopsy material that has been obtained within 28 days prior to the first dose of study drug with ALG.APV-527. Biopsy material may be provided as FFPE block or as pre-cut slides of 7 to 10 sequential tissue sections.
• Must have at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST Version 1.1.
• Must have a life expectancy of ≥3 months.
• For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective method of birth control for the duration of study treatment and for at least 9 months after the last dose of study treatment:
• Combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner

You may not qualify if:

• Has received anti-cancer chemotherapy (including molecular-targeted drugs), radiotherapy (therapeutic or curative intent) or hormonal therapy within 14 days before the first dose of ALG.APV-527; however, the following are permitted:
• Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy intended as anti-cancer ≥ 1 week prior to first dose of ALG.APV-527
• Palliative radiotherapy for bone metastases within 2 weeks prior to first dose of ALG.APV-527
• Has received immunotherapy (e.g., CAR T-cell therapy, T-cell redirecting bispecific antibodies, mono-specific antibodies, vaccines or cytokines), or investigational agents within 28 days before the first dose of ALG.APV-527.
• Has had major surgery within the 4 weeks before the first dose of ALG.APV-527.
• History of, or known, central nervous system (CNS) disease involvement (e.g., glioblastoma \[GBM\]), carcinomatous meningitis, CNS metastases including spinal metastases with a risk of spinal cord compression (spinal metastases not associated with a risk of spinal cord compression are acceptable); CNS metastases that are treated and not progressing are acceptable.
• Has seizures requiring anticonvulsant treatment or has a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
• Has uncontrolled or severe intercurrent medical condition or a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect the patient's participation in this trial.
• Has interstitial lung disease or active, non-infectious pneumonitis.
• Has a history of autoimmune disease active or past including but not limited to inflammatory bowel disease, systemic lupus erythematosus (SLE), ankylosing spondylitis, scleroderma, or multiple sclerosis. Has any active immunologic disorder requiring immunosuppression with steroids \>10mg methylprednisolone daily or its equivalent or other immunosuppressive agents (e.g., azathioprine, cyclosporine A) with the exception of patients with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave's disease. Patients with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase antibodies, and thyroid-stimulating immunoglobulin prior to study drug administration.
• Has a known hypersensitivity to a component of the protocol therapy, ALG.APV-527.
• Has a history of another primary cancer within the 5 years prior to enrollment except for the following: non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, or other non-metastatic carcinoma that has been in complete remission without treatment for more than 5 years.
• Has abnormal electrocardiograms (ECGs) that are clinically significant, such as QT prolongation (corrected QT interval \[QTcF\] \> 470 msec).

Sponsors & Collaborators

• Aptevo Therapeutics: lead
• Alligator Bioscience AB: collaborator

Study Sites (1)

Hematology Oncology Associates Of The Treasure Coast

Port Saint Lucie, Florida, 34952, United States

RECRUITING

Central Study Contacts

Caroline Taromino, MBA

CONTACT

7735749572; tarominoc@apvo.com

Study Design

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

Model Details: Escalating ALG.APV-527 doses with a starting dose of 0.1 mg/kg and projected 6 dose cohorts will be explored to determine the MTD and/or the RP2D. Part 1 consists of a 3 + 3 dose-escalation examination of ALG.APV-527 single agent therapy in adult patients with RECIST Version1.1-measurable advanced solid tumors. Part 2 consists of Dose Expansion using the RP2D, as determined during Dose Escalation.

Study Record Dates

• First Submitted: February 26, 2023
• First Posted: July 7, 2023
• Study Start: December 23, 2022
• Primary Completion: January 1, 2024
• Study Completion: December 1, 2025
• Last Updated: July 7, 2023

Record last verified: 2023-06

Locations

US (1)