To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a dose escalation, Phase 1-2 study of ABN401 in patients with advanced solid tumors, refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Abion Inc
• Collaborator: Novotech (Australia) Pty Limited

Criteria

Inclusion Criteria:

1. Signed informed consent before any study-specific screening procedures.

2. Male or female ≥ 18 years of age.

3. Body weight ≥ 40 kg and ≤ 110 kg.

4. Eastern Cooperative Oncology Group (ECOG) performance status (PS), 0 or 1

5. Must have any:

1. Histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma.

2. Refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy.

3. Metastatic breast or prostate cancer, may have bone-only disease.

6. Progressive disease (PD) on established standard medical anti-cancer therapy for his/her tumor type or intolerant to such therapy, or in the opinion of the investigator considered ineligible for a particular form of standard therapy on medical grounds.

7. At least one target lesion per response evaluation criteria in solid tumors (RECIST) 1.1, with the exception of bone-only disease (i.e. non-measurable disease per RECIST 1.1) with at least 1 radiological non-target lesion.

8. If not menopausal or surgically sterile, willing to practice at least one of the following highly effective methods of birth control for at least a (partner's) menstrual cycle before and for 3 months after study drug administration:

1. True abstinence, when this is in line with the preferred and usual lifestyle of the patient, from sexual intercourse with a member of the opposite sex.

2. Sexual intercourse with vasectomized male/sterilized female partner.

3. Hormonal female contraceptive (oral, parenteral, intravaginal, implantable, or transdermal) for at least 3 consecutive months prior to investigational product administration (when not clinically contraindicated as in breast, ovarian and endometrial cancers).

4. Use of an intrauterine contraceptive device.

9. Resolution of prior-therapy-related AEs (including immune-related AEs but excluding alopecia) to ≤ Grade 1 per CTCAE, and no treatment for these AEs for at least 2 weeks prior to the time of enrollment.

10. Minimum of 2 weeks since last dose of hormone therapy.

11. Minimum of > 2 weeks or > 5 half-lives (whichever is longer) between the start of study treatment since last dose of radiotherapy, chemotherapy or molecularly-targeted agents or tyrosine kinase inhibitors; minimum of > 3 weeks of the start of study treatment since last dose of immunotherapy/monoclonal antibodies; > 6 weeks of the start of study treatment since the last dose of nitrosoureas, antibody-drug conjugates or radioactive isotopes.

12. Adequate organ function as indicated by the laboratory values.

13. Available archival formalin-fixed, paraffin-embedded tumor tissue specimen. If patient wants to participate in the study but does not want to give the blood and tissue samples for the exploratory study, the patient might be able to participate after discussion and approval of sponsor and the medical monitor.

14. For at least one patient per dose level: Agree to pre- and on-treatment fresh tumor biopsies (that can be biopsied based on investigator's assessment) and to providing the acquired tissue for biomarker analysis. Tissue obtained for the biopsy must not be previously irradiated. No systemic antineoplastic therapy may be received by the patient between the time of the biopsy and the first administration of ABN401. An exception to the requirement for a fresh tumor biopsy in at least one patient per dose level is that if the first patient in a single dose cohort does not consent to a fresh tumor biopsy and the cohort is not expanded to 3 or 6 patients, a biopsy will not be required in that cohort. At least one fresh tumor biopsy is required in single dose cohorts that are expanded to 3 patients and in all 3+3 cohorts. Note : During pre-treatment FFPE tissue samples (unstained slides or blocks) or fresh frozen tissue can be provided for tumor analyses.

15. Able and willing to comply with the protocol and the restrictions and assessments therein.

Exclusion Criteria:

1. Previous severe hypersensitivity reaction to any component of ABN401.

2. Treatment with more than 4 lines of prior systemic therapy for recurrent/metastatic disease.

3. Chronic inflammatory liver condition. History or clinical evidence of any liver or biliary pathology including cirrhosis, infectious disease, inflammatory conditions, steatosis, or cholangitis (including ascending cholangitis, primary sclerosing cholangitis, obstruction, perforation, fistula of biliary tract, spasm of sphincter of Oddi, biliary cyst or biliary atresia).

4. Prior organ or stem cell transplant.

5. Symptomatic ascites or pleural effusion. A patient who is clinically stable for at least two weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.

6. Known active central nervous system (CNS) primary tumor or metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases and are off steroids for at least 15 days prior to first dose of study drug.

7. Known history of a hematologic malignancy, malignant primary brain tumor, or of a second malignant primary solid tumor (other than that under study), unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years.

8. Active infection requiring therapy.

9. Use of systemic corticosteroids > 10 mg/day prednisone or equivalent within 30 days or other immunosuppressive drugs within 30 days prior to start of the study.

10. Received an investigational product or treated with an investigational device within 30 days prior to first drug administration.

11. Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment; 7-day washout is permitted for palliative radiation (i.e. limited field, ≤ 14-day course of radiotherapy) to non-CNS lesions.

12. Persisting toxicity related to prior therapy (NCI-CTCAE v5 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 AEs not constituting a safety risk based on investigator's judgment are acceptable.

13. History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating e.g., rapidly progressive or uncontrolled disease involving a major organ system-vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency, or clinically significant active psychiatric or abuse disorders.

14. Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).

15. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.

16. Positive virology/serology for Human Immunodeficiency Virus (HIV)-1, HIV-2, hepatitis B (surface antigen), and hepatitis C ribonucleic acid (RNA) by polymerase chain reaction (PCR).