Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis

This is a nonrandomized, Phase 1/2 safety and tolerability study. The safety and tolerability of PRGN-2012 will be assessed following two different dose levels during the Phase 1 dose escalation trial. In the Phase 2 portion of the study, treatment with PRGN-2012 at the recommended Phase 2 dose (RP2D) will be used to determine safety and efficacy of PRGN-2012.

Inclusion criteria

• Age 18 years and older
• Clinical diagnosis of RRP

• Histological diagnosis of papilloma confirmed by pathology report from a CLIA-certified (or comparable) laboratory
• Presence of laryngotracheal papillomas with or without pulmonary RRP
• A history of 3 or more interventions in the last 12 months for control of RRP
• Clinical performance status of ECOG of 0-1
• Willing to undergo endoscopic evaluation and operative interventions with biopsies in compliance with this protocol
• No systemic therapy for RRP for at least 3 half-lives of the prior drug(s). A 30-day washout is required for systemic bevacizumab treatment
• Participants who have received prior immunotherapy for RRP are permitted
• Participants must have adequate organ and marrow function as defined below:
• Sexually active subjects (men and women) of reproductive potential must agree to use two methods of contraception: one highly effective and one other effective method throughout vaccine treatment and for at least 120 days after vaccine treatment. Highly effective methods are defined as: Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation, and partner's vasectomy; other effective methods are defined as a latex condom, diaphragm, and cervical cap.
• Seronegative for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests (Hep B DNA quant, HBV viral load), and if confirmatory tests are negative, the participant can be enrolled.
• Seronegative for hepatitis C antibody unless antigen negative. If the hepatitis C antibody test is positive, then participants must be tested for the presence of antigen by Hep C RNA quant, HCV viral load, and be HCV RNA negative
• All participants must have the ability to understand and willingness to sign a written informed consent

Exclusion criteria

• A history of surgical debridement of papillomas such that in the opinion of the study team a participant is unlikely to be able to safely have a six-week interval between clinically indicated interventions.
• History of significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (greater than or equal to New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Any severe acute or chronic medical or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, liver disease, lung disease (with the exception of what is specified in the inclusion criteria) , or laboratory abnormalities that, in the opinion of the investigators, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results and in the judgment of the investigator, would make the participant inappropriate for entry into this study. Participants with mild to moderate asthma or chronic obstructive pulmonary disease (COPD) well controlled with oral or inhaled medications are permitted to enroll.
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled, topical intranasal or intro-ocular steroids, and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Participants who are receiving any other investigational agents
• Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 5.0; however, alopecia, sensory neuropathy Grade less than or equal to 2 or other Grade less than or equal to 2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
• Known alcohol or drug abuse.
• Participant, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• History of allergy to study drug components.
• Pregnant women are excluded from this study because PRGN-2012 is an agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PRGN-2012, breastfeeding should be discontinued if the mother is treated with PRGN-2012. These potential risks may also apply to other agents used in this study.