| Eligibility |
- INCLUSION CRITERIA:
- Subjects with cytologically or histologically confirmed locally advanced not amenable
to potentially curative local therapies or metastatic human papillomavirus (HPV)
associated malignancies (Phase I only):
- Cervical cancers;
- p16+ Oropharyngeal cancers;
- Anal cancers;
- Vulvar, vaginal, penile, and squamous cell rectal cancers;
- Other locally advanced or metastatic solid tumors (e.g., lung, esophagus) that
are known HPV+.
- Subjects with cytologically or histologically confirmed newly diagnosed stage II or
III p16-positive oropharyngeal squamous cell carcinoma planned for definitive therapy
or with newly diagnosed stage II or III or IVA or IVB HPV-positive sinonasal squamous
carcinoma (HPV-SNSCC) eligible for primary surgery (Phase II only).
- Subjects must have measurable disease, per Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 (Phase 1 only).
- Phase I only: Participants must have received one prior line of systemic chemotherapy
in the recurrent/metastatic setting as well as checkpoint blockade therapy in tumors
with Food and Drug Administration (FDA) approval (head and neck squamous cell cancer
and programmed death-ligand 1 (PDL1+) cervical cancer). Exceptions to this include
participants not eligible to receive standard therapy.
- Men or Women; Age >=18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Adequate hematologic function at screening, as follows:
- Absolute neutrophil count (ANC) >=1 x 109/L;
- Hemoglobin >= 9 g/dL;
- Platelets >= 75,000/microliter.
- Adequate renal and hepatic function at screening, as follows:
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR Measured or calculated
creatinine clearance >= 40 mL/min for participant with creatinine levels > 1.5 X
institutional ULN (GFR can also be used in place of creatinine or CrCl);
- Bilirubin =< 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin
=< 3.0 x ULN;
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN,
unless liver metastases are present, then values must be =< 3 x ULN).
- The effects of the immunotherapies (PRGN-2009 vaccine and M7824) on the developing
human fetus are unknown. For this reason and because M7824 and PRGN-2009 used in this
trial are possibly teratogenic, women of child-bearing potential and men must agree to
use highly effective contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and up to 2 months following the last dose of M7824
study treatment. Should a woman become pregnant or suspect she is pregnant while she
or her partner is participating in this study, she should inform her treating
physician immediately.
- Participants serologically positive for human immunodeficiency virus (HIV), Hep B, Hep
C are eligible as long as the viral loads are undetectable by quantitative polymerase
chain reaction (PCR). HIV positive participants must have cluster of differentiation 4
(CD4) count >= 200 cells per cubic millimeter at enrollment, be on stable
antiretroviral therapy for at least 4 weeks and have no reported opportunistic
infections or Castleman's disease within 12 months prior to enrollment.
EXCLUSION CRITERIA:
- Participants with prior investigational drug, live vaccine, chemotherapy,
immunotherapy or any prior radiotherapy (except for palliative bone directed therapy)
within the past 28 days prior to the first drug administration except if the
investigator has assessed that all residual treatment-related toxicities have resolved
or are minimal and feel the participant is otherwise suitable for enrollment.
Participants may continue adjuvant hormonal therapy in the setting of a definitively
treated cancer (e.g., breast).
- Major surgery within 28 days prior to the first drug administration (minimally
invasive procedures such as diagnostic biopsies are permitted).
- Known active brain or central nervous system metastasis (less than a month out from
definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (<3
months) or clinically significant cerebrovascular accident (<3 months). In order to be
eligible participants must have repeated central nervous system (CNS) imaging at least
a month after definitive treatment showing stable CNS disease. Participants with
evidence of intra-tumoral or peritumoral hemorrhage on baseline imaging are also
excluded unless the hemorrhage is grade =< 1 and has been shown to be stable on two
consecutive imaging scans.
- Pregnant women are excluded from this study because M7824 and PRGN-2009 vaccine have
not been tested in pregnant women and there is 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 these
immunotherapies, breastfeeding should be discontinued if the mother is treated on this
protocol.
- Only for Phase I, Arm 1B: Active autoimmune disease that might deteriorate when
receiving an immunostimulatory agent with exception of:
- Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid
disease or other mild autoimmune disorders not requiring immunosuppressive
treatment;
- Administration of steroids for other conditions through a route known to result
in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation)
is acceptable;
- Subjects on systemic intravenous or oral corticosteroid therapy with the
exception of
physiologic doses of corticosteroids (=< the equivalent of prednisone 10 mg/day) or other
immunosuppressors such as azathioprine or cyclosporin A are excluded on the basis of
potential immune suppression. For these subjects these excluded treatments must be
discontinued at least 1 weeks prior to enrollment for recent short course use (=< 14 days)
or discontinued at least 4 weeks prior to enrollment for long term use (> 14 days). In
addition, the use of corticosteroids as premedication for contrast-enhanced studies is
allowed prior to enrollment and on study.
- Only for Phase I: Subjects with a history of serious intercurrent chronic or acute
illness, such as cardiac or pulmonary disease, hepatic disease, bleeding diathesis or
recent (within 3 months) clinically significant bleeding events, known left
ventricular ejection fraction <50% (confirmation of ejection fraction (EF) > 50% is
not required for eligibility), history of myocarditis, or recent myocardial infarction
(within 6 months), or other illness considered by the Investigator as high risk for
M7824 drug treatment.
- Only for Phase I: Subjects refusing to accept blood products as medically indicated.
- History of second malignancy within 3 years of enrollment except for the following:
adequately treated localized skin cancer, cervical carcinoma in situ, superficial
bladder cancer, other localized malignancy which has been adequately treated or
malignancy which does not require active systemic treatment (e.g., low risk chronic
lymphocytic leukemia (CLL)). For participants enrolled on the phase I portion of the
protocol a second HPV driven malignancy is allowed.
- Only for Phase I, Arm 1B: Subjects with a known severe hypersensitivity reaction to
monoclonal antibodies or its excipients (grade >/= 3 National Cancer Institute
(NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5) will be evaluated by
the allergy/immunology team prior to enrollment.
- Prior allogenic tissue/solid organ transplant.
- For participants who may receive M7824: previous life-threatening side effects
resulting from prior checkpoint inhibitor therapy.
- Participants with pulse oximetry < 92% on room air at screening.
- Participants unable to provide informed consent.
- Participants whose inclusion in the trial would in the judgement of the principal
investigator (PI) lead to time from diagnosis to initiation of curative treatment
of>70 days (Arm 2A only).
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