Trial Outcomes & Findings for HPV Vaccine PRGN-2009 Alone or in Combination With Anti-PDL1/TGF-Beta Trap (M7824) in Subjects With HPV Associated Cancers (NCT NCT04432597)

HPV Vaccine PRGN-2009 Alone or in Combination With Anti-PDL1/TGF-Beta Trap (M7824) in Subjects With HPV Associated Cancers

Phase I: To determine the recommended phase II dose (RP2D) of PRGN-2009 Human Papillomavirus Vaccine (HPV) vaccine alone or in combination with M7824 (MSB0011359C). Recommended Phase 2 Dose, the dose of a drug or drug combination that was identified in a Phase 1 study (dose finding study) that was identified for continued study.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. All participants who receive any investigational treatment will be evaluable for safety and toxicity evaluations.

CD3+ tumor infiltrating T cells post treatment compared with pre-treatment reported with a 95% confidence interval assessed by multiplex CD3+ tumor infiltrating lymphocytes assessed by multiplex immunofluorescence from the surgical/ biopsy tissue collected pre- and post-treatment. The percentage of participants with doubling of baseline CD3+ tumor infiltrating lymphocytes will be provided as well as the 95% confidence interval. The CD3 cells are assessed by multiplex immunofluorescence in the biopsies. Doubling is the desired outcome.

Phase I: proportion of participants that are hospitalized because of adverse events attributed to disease progression. Adverse events were assessed by the Common Terminology Criteria for Adverse Events(CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors(RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progression.

Phase II: Overall survival assessed using the Kaplan-Meier method, defined as the time from the date of first treatment to the date of death (any cause). Participants who receive two doses of PRGN-2009 and go on to receive standard definitive therapy will be evaluable for overall survival assessment.

Phase II: 3-year Relapse-free survival assessed using the Kaplan-Meier method, defined as the time from completion of standard of care definitive therapy to the date of disease recurrence or death (any cause) whichever occurs first. Participants who receive two doses of PRGN-2009 and go on to receive standard definitive therapy will be evaluable for overall survival assessment.

Phase I: Overall survival assessed using the Kaplan-Meier method, defined as the time from the date of first treatment to the date of death (any cause). Participants who are alive at the end of follow up will be censored at the last known date alive.

PFS, evaluated using Kaplan-Meier methods, defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurs first. Disease progression assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression.

Phase 1: DOR is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression.

Phase II: Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. All participants who receive any investigational treatment will be evaluable for safety and toxicity evaluations.

Phase II: Assess if PRGN-2009 results in significantly prolonged survival at three years as compared to the expected 80% three-year historical survival in p16-positive oropharyngeal cancer (OPC) participants. Three-year overall survival will be measured using a Kaplan-Meier curve and will be compared descriptively with the historical benchmark. Participants who receive two doses of PRGN-2009 and go on to receive standard definitive therapy will be evaluable for overall survival assessment.

Phase 1: overall response rate (ORR) accessed according to the Response Evaluation Criteria in Solid Tumors (RECIST)1.1., defined as a complete response or partial response assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

DLT is defined as any one of the following adverse events, possibly attributable to study drugs, that occur within 28 days of the human papillomavirus (HPV) vaccine monotherapy or 28 days of starting the HPV vaccine + M7824 (MSB0011359C) combination therapy: any grade 3 or higher bleeding episode requiring blood transfusion(s); Any Grade 4 or \> adverse drug reactions (ADRs) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and assessed as possibly related to any agent by the Investigator, except for laboratory values that are asymptomatic or resolve to Grade ≤ 1 or baseline grade within 7 days without medical intervention; discontinuation any Grade 3 ADRs possibly attributed to any agent except for any of the following: Grade 3 flu-like symptoms or fever, as well as associated symptoms of fatigue, headaches, nausea, emesis which can be controlled with conservative medical management. See Protocol for details.