AVA-1207 Open Label study in patients with therapy refractory metastatic castration resistant prostate cancer

Phase 1

• Conditions: Prostate Cancer; MedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-001789-39-ES
• Lead Sponsor: AVA Therapeutics N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-03-11
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 66

Inclusion Criteria

Patients are eligible to be included in the trial only if all of the following criteria apply:
1. Patient must be 18 years of age inclusive or above, at the time of signing the informed consent.
2. Male patient with mCRPC as defined by PCWG3 criteria (histologically confirmed adenocarcinoma; adenocarcinoma with =10% small-cell or neuroendocrine features is allowed). Brain metastasis are allowed as long as the patient’s symptoms are well controlled.
3. Patient should have failed at least 1 line of taxane-based chemotherapy or is deemed medically unsuitable to be treated with a taxane regimen.
4. Patient should have received a 2nd generation or later androgen receptor targeted therapy/ androgen biosynthesis inhibitor (e.g. abiraterone, enzalutamide, and/or apalutamide). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting.
5. Patients will be unlikely to tolerate or derive clinically meaningful benefit from other available therapy.
6. Patients for which any drug related toxicity adverse effects of any prior cancer therapy should have resolved to Grade 1 or less according CTCAE v5.0 or to baseline severity level.
7. Patients with evidence of progressive disease, defined as 1 or more criteria:
a. PSA level =1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.
b. Computed tomography (CT) or magnetic resonance imaging (MRI) scan: nodal or visceral
progression as defined by RECIST 1.1.
c. Bone scintigraphy: appearance of 2 or more new metastatic lesions.
8. Patient should have undergone bilateral orchiectomy or should be on continuous androgen-deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist or antagonist (surgical or medical castration).
9. Total serum testosterone = 50 ng/dL or 1.73 nmol/L.
10. Measurable or evaluable disease:
Part 1-Dose escalation: Either measurable or evaluable disease for prostate cancer.
Part 2-Expansion cohort: At least one measurable lesion as per RECIST v1.1.
11. Predicted life-expectancy of = 6 months.
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
13. Adequate renal (estimated glomerular filtration rate [eGFR] per local laboratory> 40 mL/min/1.73m2), hepatic (bilirubine 1 x109/L,
platelet count > 75x109/L).
14. Males who are:
a. Surgically sterile (bilateral orchiectomy, vasectomy)
b. Compliant with an effective contraceptive regimen (i.e. use of male condom with female partner and assuring use of an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant following from signing of the informed consent form [ICF] through 90 days after the last IMP administration) from signing of the ICF through 90 days after the last IMP administration). Abstinence is not considered an adequate contraceptive regimen.
c. Refraining from donating sperm following from signing of the ICF through 90 days after the last IMP administration.
15. Capable of giving signed and dated informed consent prior to initiation of any trial-related procedures that are not considered Standard of Care which includes compliance with the requir

Exclusion Criteria

Patients are excluded from the trial if any of the following criteria apply:
1. Other malignancies within the last 2 years except adequately treated carcinoma in situ, basal or squamous cell skin carcinoma.
2. Uncontrolled or severe intercurrent medical condition.
3. Positive serological testing for human immunodeficiency virus (HIV) antibody.
4. Positive serological hepatitis B surface antigen [HBsAg] and hepatitis B core antibody (anti-HBc) negative, and hepatitis C virus antibody. Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative polymerase chain reaction (PCR) within 6 weeks prior to initial IMP administration. Those who are PCR positive will be excluded.
5. Patient has any active-, uncontrolled-, or suspected infection.
6. Known clinically relevant immunodeficiency disorders.
7. 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 participation in this trial.
8. Unstable cardiovascular function defined as: (a) symptomatic ischemia, or (b) uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block is not excluded), or (c) congestive heart failure New York Heart Association Class = 3, or (d) myocardial infarction within 3 months.
9. Previous treatment with antitumor therapies 2 weeks prior to initial IMP for radiotherapy and 4 weeks for systemic chemotherapy or poly (ADP-ribose) polymerase (PARP) inhibitor.
10. Previous treatment with live or live attenuated vaccines within 2 weeks prior to initial IMP administration. New types of vaccines need to be evaluated as to their mode of action.
11. Treatment with other investigational agents in the 4 weeks prior to initial IMP.
12. Major surgery within 4 weeks prior to dosing.
13. Hypersensitivity to any of the excipients present in the IMP.
14. Previous treatment with any systemic immunosuppressant within 4 weeks prior to initial IMP administration, with the exception of systemic corticosteroid use up to oral dose of 10 mg prednisone daily (or equivalent for other steroids).
15. Previous treatment with an aminobisphosphonate IV (e.g. ibandronate, pamidronate, zoledronate etc) within 4 weeks prior to initial IMP.
16. Part 2 only: previous treatment with (and progression on) a PSMA targeting agents.
17. Known ongoing drug and alcohol abuse in the opinion of the investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified