Galinpepimut-S in Combination With Pembrolizumab in Patients With Selected Advanced Cancers

Inclusion Criteria

• •Is willing and able to understand and provide signed informed consent for the study that fulfills IRB guidelines
• •Male or female patients \>18 years of age on the day of signing informed consent
• •Histologically or cytologically-confirmed advanced or metastatic solid tumors who have disease progression after treatment with available therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment in the context of the particular line of treatment or, specifically for AML, demonstrate as their best response after 4 cycles of HMA therapy the status of "partial response" per European LeukemiaNet (ELN) criteria and meet the additional specified requirements for the cohort of the study they will enroll into.
• •All patients in the solid tumor arms will be tested for WT1 expression via IHC in their initial primary tumor OR recent biopsy of metastatic disease at the time of screening for study entry. Specifically for AML, patients will be tested for WT1 expression via IHC in their leukemic blasts either in the BM or PB. Assessment of WT1 expression positivity will be performed via central review prior to study entry.
• •Patients may have received a specific maximum allowable number of prior lines of therapy for metastatic disease, as follows: CRC: 2 or 3 lines; OvC: 1 or 2 lines; SCLC: 1 line; TNBC: 1 line; and AML: 1 line (allo-SCT-eligible status not allowed)
• •For solid tumor arms: patients must measurable disease based on RECIST v1.1 as determined by the local study team.
• •For AML arm, eligibility is defined as:
• •1. Prior frontline (1st line) with HMAs since initial AML diagnosis;
• •2. Prior cytoreductive therapy with hydroxyurea or leukapheresis at the time of initial diagnosis, with subsequent immediate seamless transitioning to HMA therapy
• •3. History of induction early failure after initial therapy with up to 2 cycles of standard chemotherapy ("7+3" or similar regimen), with subsequent immediate seamless transitioning to HMA therapy as long as patients have achieved PR as their best observable response after 4 cycles of HMA therapy; HMA therapy continues throughout the trial period.
• •Resolution of toxicity effect(s) from most recent prior chemotherapy to Grade 1 or less (except alopecia). If the patient received major surgery or radiation therapy of \> 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
• •(ECOG) performance status of 0 or 1.
• •For women of child-bearing potential, agreement to use adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)
• •Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 4 months following the last study treatment.
• •Have adequate organ function as defined:
• •* Absolute neutrophil count (ANC) ≥1500/µL
• •* Platelets ≥100,000/µL
• •* Hemoglobin (Hb) ≥9.0 g/dL or ≥5.6 mmol/L (N.B.: Hb criterion must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks)
• •* Creatinine ≤1.5 × upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for subjects with creatinine levels \>1.5 × institutional ULN
• •* Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for subjects with total bilirubin levels \>1.5 × ULN
• •* AST (SGOT) and ALT (SGPT) ≤2.5 × ULN OR ≤5 × ULN for subjects with liver metastases
• •* International normalized ratio (INR) OR prothrombin time (PT) and Activated partial thromboplastin time (aPTT) ≤1.5 × ULN, unless subjects are receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range of intended use of anticoagulants
• •(i).Colorectal Cancer (third/fourth line)
• •Histologically or cytologically documented adenocarcinoma of colon or rectum at the time of initial presentation.
• •Metastatic CRC with documented disease progression (per standard criteria) after the last administration of standard therapies or intolerance to standard therapies (and approved therapies must have included all the following a fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and, if KRAS wild-type, cetuximab or panitumumab). Prior use of and failure after regorafenib or trifluridine/tipiracil is allowed but not mandated.
• •(ii). OvC (second/third line)
• •Histologically diagnosed ovarian, fallopian tube or primary peritoneal cancer at the time of initial presentation.
• •Patients will have either relapsed or be disease resistant to their prior therapy. Interval surgery is permitted, but patients must have objective evidence of disease on computed tomography (CT)or magnetic resonance imaging (MRI), with concomitant CA-125 increase and/or biopsy showing OvC (only for recurrent disease).
• •Patients should have received platinum-containing chemotherapy and been designated as harboring platinum-refractory or -resistant disease. Additionally, all eligible subjects should have either received (or been offered) bevacizumab therapy, and those with BRCA germline mutations (gBRCA mut) should have been offered therapy with poly-ADP ribose polymerase (PARP) inhibitors (olaparib, rucaparib or niraparib).
• •(iii). SCLC (second line)
• •Histologically or cytologically confirmed SCLC based on biopsy of the tumor at initial presentation.
• •Asymptomatic or treated brain metastases are allowed.
• •Patients must have measurable disease (by CT or MRI) after they progressed or were resistant to 1 prior systemic therapy.
• •(iv). TNBC (second line)
• •Histologically proven metastatic breast carcinoma with triple negative receptor status.
• •TNBC status is defined as estrogen and progesterone receptor negative by IHC, and human epidermal growth factor receptor 2 \[HER2\] negative by IHC AND HER2 gene non-amplified by fluorescence in situ hybridization \[FISH\], per standard criteria. Patients who are weakly positive for the estrogen or progesterone receptor (i.e., \< 5%) are eligible.
• •Patients must have measurable disease(by CT or MRI) after they progressed or were resistant to 1 prior systemic therapy.
• •Patients have undergone second-line therapy after residual or recurrent disease after first-line therapy. The latter may have included:
• •1. Neoadjuvant therapy if macroscopic disease was still present after surgery OR
• •2. Adjuvant therapy, but only if the macroscopic relapse occurred \> 6 months from the start of study treatment with pembrolizumab.
• •(v). AML
• •Pathologically or morphologically confirmed de novo or secondary AML at the time of initial diagnosis.
• •Achievement of no better than morphologic PR, as defined initially by the AML Working Group criteria (Cheson et al,2003), and also quoted in the more recent ELN criteria (Döhner et al, 2010),while on active treatment with HMAs.
• •AML patients are eligible only if they received first-line therapy with HMAs (decitabine or azacytidine) for 4 cycles and achieved only PR at the end of cycle 4.
• •AML patients must remain on HMA therapy throughout the trial.