Clinical trial NCT05553639: HB-302/HB-301 Therapy in Participants With Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 1/2 Study of Replicating Arenavirus-based Vector(s) Encoding Prostate Cancer-Associated Antigens in Participants With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer Metastatic
Keywords: Prostate
Prostate Cancer
Metastatic
Metastatic Cancer
Metastatic Prostate Cancer
Castration Resistant
Castration Resistant Prostate Cancer
mCRPC
CRPC
Vaccine
Viral Vector
Viral Therapy
Immunotherapy
Vaccine Therapy
Lead sponsor: Hookipa Biotech GmbH
Sponsor class: INDUSTRY
First posted: 2022-09-23
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a first-in-human Phase 1/2, multinational, multicenter, open-label study of HB-302/HB-301 alternating 2-vector therapy in participants with metastatic castration-resistant prostate cancer (mCRPC) comprising 2 phases: a Phase 1 Dose Escalation and recommended Phase 2 dose (RP2D) Confirmation, and a Phase 2 Dose Expansion.

Detailed description: This is a first-in-human Phase 1/2, multinational, multicenter, open-label study of HB-302/HB-301 alternating 2-vector therapy in participants with metastatic castration-resistant prostate cancer (mCRPC) comprising 2 phases: a Phase 1 Dose Escalation and recommended Phase 2 dose (RP2D) Confirmation, and a Phase 2 Dose Expansion.

The Phase 1 Dose Escalation will evaluate HB-302/HB-301 alternating 2-vector therapy for safety and tolerability, preliminary efficacy and immunogenicity, and determination of a safe recommended Phase 2 dose (RP2D). A confirmatory cohort (or cohorts) will inform the determination of the RP2D. The Phase 2 Dose Expansion will assess HB-302/HB-301 alternating 2-vector therapy at the RP2D defined in the Phase 1 part of the study.

Study drugs HB-301 and HB-302 are genetically-engineered replicating vectors based on the arenavirus lymphocytic choriomeningitis virus (LCMV) and arenavirus Pichinde virus (PICV), respectively. HB-301 and HB-302 express the same transgenes encoding 2 prostate cancer-associated antigens: prostatic acid phosphatase (PAP) and prostate specific antigen (PSA). HB-302/HB-301 Alternating 2-vector therapy will be administered intravenously every 3 weeks (Q3W) for the first 5 doses and every 6 weeks (Q6W) from the fifth dose and onward. HB-302 is to be administered first followed 3 or 6 weeks later by HB-301.

In total, approximately 70 participants aged 18 years and older will be enrolled in this study to receive HB-302/HB-301 alternating 2-vector therapy.

About 40 Investigators and study sites in the United States (US) and Europe are expected to participate in this study.

Eligibility criteria: Inclusion Criteria:

1. Male participants ≥18 years of age on day of signing the informed consent form (ICF)
2. Confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, and evidence of metastatic disease.
3. Documented castration-resistant disease with serum level of testosterone \<50 ng/dL (1.7 nmol/L).
4. Have been treated with at least one second-generation androgen receptor signaling inhibitor (ARSI) (e.g., enzalutamide)

   * No prior chemotherapy regimens are permitted (docetaxel in the castration-sensitive setting is acceptable)
   * Participants must have had disease progression on SOC therapy assessed by the Investigator.
   * Antiandrogen/ARSI withdrawal must take place at least 2 weeks before enrollment unless agreed otherwise between the Sponsor and the Investigator. LHRH agonists or antagonists should be continued.
5. Must have ≥1 metastatic lesion that is present on baseline imaging

   * Participants with liver metastasis are not eligible to enroll in this study
   * Participants with only bone metastasis present at baseline are eligible to enroll in this study
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
7. Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks prior to study drug administration.
8. Screening laboratory values must meet the criteria for adequate organ function that will be decided by the investigator.

Exclusion Criteria:

1. Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation or study treatment administration, impair the ability of the participant to receive study treatment, or interfere with the interpretation of the study results. This includes clinically significant (i.e., active) cardiovascular disease, including cerebral vascular accident/stroke and myocardial infarction less than 6 months prior to enrollment, unstable angina, congestive heart failure (New York Heart Association Classification Class II), or serious uncontrolled cardiac arrhythmias (including prolonged corrected QT interval, uncontrolled atrial fibrillation, etc.)
2. Uncontrolled pain or uncontrolled symptoms related to worsening of underlying disease or symptomatic bone metastasis.
3. An active autoimmune disease that has required systemic treatment in past 2 years.

   • Note: 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.
4. Has received the following immunosuppressive or systemic replacement medication:

   * Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses \>10 mg/day prednisone or equivalent), within 14 days of the first administration of study treatment.

     • Note: inhaled or topical steroids and adrenal replacement in doses equivalent to \>10 mg/day prednisone are permitted in the absence of active autoimmune disease.
   * Any chronic immunosuppressive medication within 6 months prior to the first administration of study treatment (unless agreed otherwise between the Sponsor and the Investigator on a case-by-case basis).
5. Has received a live or live-attenuated vaccine within 30 days of planned start of study therapy, unless agreed otherwise between the Sponsor and Investigator.

   • Administration of non-live vaccines is allowed.
6. Currently participating in or has participated in a study of an investigational agent or has used an investigational device treatment, within 4 weeks prior to the first dose of treatment.
7. Allogeneic tissue/solid organ transplant (e.g., allogeneic stem cell transplantation, xenogeneic transplant).
8. Active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or epidural or neurological metastasis.
9. Active infection requiring systemic therapy.
10. Positive COVID-19 test in 6 weeks prior to the enrollment.
11. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
12. Known history of Hepatitis B (HBV) (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C (HCV) infection (defined as HCV ribonucleic acid \[RNA\] is detected \[qualitative\]).
13. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Primary outcomes:
measure: Phase I
timeFrame: 1. First 42 days of treatment, 2. Approximately 6 months
measure: Phase II
timeFrame: Up to 2 years
Secondary outcomes:
measure: Phase I
timeFrame: Approximately 2 years
measure: Phase II
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research & Excellence (cCARE)
state: California
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: New Brunswick
country: United States
facility: The Cancer Institute of New Jersey CINJ Rutgers
state: New Jersey
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
Study officials:
affiliation: Hookipa Biotech GmbH
name: Head of Clinical Development
role: STUDY_DIRECTOR
References: