Purpose

This is an First in Human (FIH) Phase I/II, multinational, multicenter, open-label study of HB-201 monotherapy and HB-201 & HB-202 combination therapy in patients with HPV 16+ confirmed cancers comprising two parts: Phase I Dose Escalation and Phase II Dose Expansion.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

All Patients:

1. Male or female patients 18 years of age, or older, at the time of signing the Informed Consent Form (ICF).

2. Patient must have ≥ 1 measurable lesion by computed tomography (CT) and/or magnetic resonance imaging (MRI), that will be assessed for tumor response following RECIST and immune Response Evaluation Criteria in Solid Tumors (iRECIST) during study conduct.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

4. Prior curative radiation therapy must have been completed ≥ 4 weeks prior to study treatment administration. Prior focal palliative radiotherapy must have been completed ≥ 2 weeks prior to study treatment administration.

5. Screening laboratory values must meet the following criteria and should be obtained within 28 days prior to study treatment administration.

6. Able to understand and willing to comply with study procedures, restrictions, and requirements, in the opinion of the Investigator.

7. Willing and able to give voluntary informed consent for participation in the study.

Treatment Group 1, Group 3, Group A, or Group D

8. Patient must have documentation of confirmed HPV 16+ HNSCC via genotype testing as specified.

9. Patient must have had tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy, (e.g., failed platinum-based therapy and/or PD L1 therapy) or be a patient for whom standard of care therapy is contraindicated.

10. Tumor tissue (archival [no older than two years] or able to provide fresh biopsy specimen during Screening) collected following the patient's progression from the last treatment,unless agreed otherwise between the Sponsor and the Investigator.

Treatment Group 2, Group 4, Group C, or Group F, if IT administration of the dose level explored is not feasible

11. Documentation of confirmed HPV 16+ cancer (of any origin) via genotype testing as specified.

12. Patients who have had tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy, or for patients for whom standard of care therapy is contraindicated.

13. Patient must have a safe and accessible tumor site amenable for biopsy and IT administration, unless agreed otherwise between the Sponsor and the Investigator.

14. Apart from the tumor site(s) amenable for biopsy and IT administration, the patient must have ≥ 1 measurable lesion, that will be assessed for tumor response following RECIST and iRECIST during study conduct.

Treatment Group 2, Group 4, Group C, or Group F, without intratumoral administration

15. Documentation of confirmed HPV 16+ non-HNSCC cancer via genotype testing as specified.

16. Patients who have had tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy, or for patients for whom standard of care therapy is contraindicated.

17. Tumor tissue (archival [no older than two years] or able to provide fresh biopsy specimen during Screening) collected following the patient's progression from the last treatment,unless agreed otherwise between the Sponsor and the Investigator.

Treatment Group B or Group E

18. Documentation of confirmed HPV 16+ HNSCC via genotype testing as specified.

19. Patient must be eligible, as per standard of care, to receive nivolumab (i.e., naïve to PD L1 therapy and have progressed on platinum-based therapy).

20. Tumor tissue (archival [no older than 2 years] or able to provide fresh biopsy specimen during Screening) collected following the patient's progression from the last treatment,unless agreed otherwise between the Sponsor and the Investigator.

Contraceptive Criteria (all groups):

21. Female patients who are of childbearing potential must have a negative serum β human chorionic gonadotrophin (β-hCG) pregnancy test prior to the first administration of study treatment or be surgically/biologically sterile (hysterectomy or bilateral oophorectomy) or postmenopausal.

22. Patients must agree to refrain from sperm and egg donation from the time period between signing of the ICF and through five months after the last dose of study drug.

23. Female patients of childbearing potential can participate in the study if they agree to use highly effective contraception from signing of the ICF through five months after the last study treatment administration.

24. Male patients with sexual partners of childbearing potential can participate in the study if they agree to use barrier contraception from signing of the ICF through five months after the last study treatment administration.

Exclusion Criteria

All Patients:

1. Patients with untreated and/or symptomatic metastatic central nervous system (CNS) disease. However, patients with brain/CNS metastases who have undergone surgery or radiotherapy, whose disease is stable and who have been on a stable dose of corticosteroids (≤ 10 mg prednisone or equivalent) for ≥ 4 weeks prior to the first administration of study treatment will be eligible.

2. 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 patient 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 six months prior to enrollment, unstable angina, congestive heart failure (New York Heart Association Classification Class II), or serious uncontrolled cardiac arrhythmias.

3. Concurrent malignancy that is clinically significant or requires active intervention at the time of Screening (with the exception of adequately treated, basal or squamous cell carcinoma, non melanomatous skin cancer), unless agreed otherwise between the Sponsor and the Investigator.

4. Active, known or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy, with the exception of low dose prednisone (≤ 10 mg or equivalent).

The following are exceptions to this criterion:

- Patients with vitiligo or alopecia.

- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.

- Any chronic skin condition that does not require systemic treatment.

5. All toxicities attributed to systemic prior anticancer therapy other than alopecia and fatigue that have not resolved to Grade 1 or baseline prior to the first administration of study treatment. Patients with toxicities attributed to systemic prior anticancer therapy, which are not expected to resolve and result in long lasting sequelae, such as neuropathy or ototoxicity after platinum-based therapy, are permitted to enroll.

6. Treatment with any chemotherapy, biological, or investigational therapy for cancer within 28 days of the first administration of study treatment.

7. Treatment with 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.

8. Treatment with any chronic immunosuppressive medication within six months prior to the first administration of study treatment.

9. Patients who have had a prior anaphylactic or other severe reaction to human immunoglobulin or antibody formulation administration.

10. Live vaccines within 28 days prior to the first dose of study treatment.

11. Herbal remedies with immune stimulating properties or known to potentially interfere with major organ function within 28 days prior to the first dose of study treatment.

12. Female patients who are pregnant, breastfeeding, or plan on becoming pregnant during the study.

13. Positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody, indicating acute or chronic infection. Patients who test positive for HCV antibody but negative for HCV ribonucleic acid (RNA) are permitted to enroll.

14. Known history of acquired immunodeficiency syndrome. Testing for the human immunodeficiency virus is not mandatory.

15. Other concurrent severe and/or uncontrolled medical conditions that would, in the Investigator's judgment, contraindicate participation in this study.

16. Psychological, familial, sociological, or geographical conditions that do not permit medical follow-up and compliance with the study protocol.

Dose Expansion Only: Patients Who Qualify to Receive Nivolumab as Part of Standard of Care Treatment

17. History of severe hypersensitivity reaction to nivolumab.

18. Significant advanced pulmonary disease at Screening

19. History of untreated tuberculosis.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Ph I, Group 1 HB-201 IV only
HB-201 as an IV administration in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • Drug: HB-201 intravenous administration
    Dose Expansion
Experimental
Ph I, Group 2 HB-201 IT-IV
HB-201 as an IT administration for the first dose, followed by HB-201 as an IV administration for the subsequent doses in patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • Drug: HB-201 intratumoral administration on first cycle, followed by HB-201 intravenous administration on subsequent cycles
    Dose Expansion
Experimental
Ph I, Group 3 HB-202 IV + HB-201 IV
HB-202 as an IV administration (initial) and then alternating with HB-201 IV administration in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration
    Dose Escalation based on 3+3 dose escalation (3 to 6 patients per cohort).
Experimental
Ph I, Group 4 HB-201 IT, followed by HB-202 IV + HB-201 IV
HB-201 as an IT administration for the first dose, and then alternating with HB-202 IV and HB-201 IV administration each cycle in patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • Drug: HB-201 intratumoral administration on first cycle, followed by HB-202 intravenous administration alternating with HB-201 intravenous
    Dose Escalation based on 3+3 dose escalation (3 to 6 patients per cohort).
Experimental
Ph II, Group A-HB-201 IV only
HB-201 as an IV administration in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • Drug: HB-201 intravenous administration
    Dose Expansion
Experimental
Ph II, Group B HB-201 IV only + nivolumab
HB-201 administered IV with nivolumab in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care and are eligible to receive nivolumab.
  • Drug: HB-201 intravenous administration + nivolumab
    Dose Expansion
Experimental
Ph II, Group C HB-201 IT-IV
HB-201 as an IT administration for the first dose, followed by HB 201 as an IV administration for the subsequent doses in patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • Drug: HB-201 intratumoral administration on first cycle, followed by HB-201 intravenous administration on subsequent cycles
    Dose Expansion
Experimental
Ph II, Group D with alternating HB-202 IV and HB-201 IV
Sequential alternating administrations of HB 202 IV and HB 201 IV in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • Drug: Alternating HB-202 IV and HB-201 IV
    Dose Expansion
Experimental
Ph II, Group E HB-202 IV and HB-201 IV + nivolumab
Sequential alternating administrations of HB-202 IV and HB-201 IV, and nivolumab in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy and are eligible to receive nivolumab.
  • Drug: HB-202 IV and HB-201 IV + nivolumab
    Dose Expansion
Experimental
Ph II, Group F HB-201 IT & alternating HB-202 IV & HB-201 IV
Administration of HB-201 IT for the first dose, followed by sequential alternating administrations of HB-202 IV and HB-201 IV patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • Drug: HB-201 IT & alternating HB-202 IV & HB-201 IV
    Dose Expansion

Recruiting Locations

Montefiore-Einstein Center for Cancer Care
Bronx, New York 10461
Contact:
Sanjay Goel, MD

More Details

Status
Recruiting
Sponsor
Hookipa Biotech

Study Contact

General Hookipa contact
+43 1 890 6360
office@hookipabiotech.com

Detailed Description

The Phase I Dose Escalation will comprise two treatment groups (Groups 1 and 2) of HB-201 monotherapy and two treatment groups (Groups 3 and 4) of HB-201 & HB-202 dual drug regimen. Group 1 and Group 2 Phase I Dose Escalation will determine a safe recommended Phase II dose (RP2D) of HB- 201 for intravenous (IV) and intratumoral (IT) treatment. Group 3 and Group 4 Phase I Dose Escalation will determine a safe RP2D of HB-202 for IV.

The Phase II Dose Expansion may have up to six treatment groups (Groups A to F). Groups A will consist of HB-201 monotherapy administered IV , Group B will consist of HB-201 monotherapy administered IV in combination with an immune checkpoint inhibitor ; Group C will consist of HB-201 monotherapy as an IT administration for the first dose, followed by HB-201 monotherapy as an IV administration; Group D will be Sequential and alternating administrations of HB-202 IV and HB-201 IV; Group E will be sequential and alternating administrations of HB-202 IV and HB-201 IV with an immune checkpoint inhibitor; Group F will be the administration of HB-201 monotherapy IT for the first dose, followed by a sequential alternating administration of HB-202 IV and HB-201 IV.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.