Effective strategies to prolong remission or to prevent relapse are required (Hoskins WJ et al, 2005). With regard to immunotherapy approaches in OvC, immunization against tumor-associated antigens (TAA) lead to emergence of both TAA -specific antibodies and T-cell effectors have been shown to provide benefit in OvC models. Antibodies have been noted to curtail early tissue invasion (Zhang H et al, 1998). Preclinical models have also demonstrated the clearance of circulating tumor cells and the elimination of systemic micrometastasis through the use of both passively administered and vaccine-induced antibodies. With regards to T -cell effectors, a globally activated immune response has been shown to be associated with improved clinical outcome in patients with advanced OvC. Zhang et al showed that the presence of tumor infiltrating T cells within tumor cell islets was associated wi th improvement in both progression free and OS (Zhang H et al, 2003). Conversely, the infiltration of T - regulatory cells confers a worse prognosis (Curiel TJ et al, 2004). OvC patients in second or greater remission confirms them to relapse in a predicta ble fashion (Iasonos A et al, 2012) and, therefore, are candidates for novel immune -based SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 101 “consolidation” strategies, such as those including checkpoint inhibitors and TAA -directed immunizing vaccine-type therapies, like galinpepimut-S, either alone or in combination. The strong expression of WT1 protein in OvC coupled with its proposed mechanism of action makes it a rational target for immunotherapy. WT1 expression is highly prevalent in OvC (Dupont et al, 2004). Indeed, WT1 expression is high enough that pathologists routinely use IHC stains for WT1 with a standardized convention for describing expression and determining as “positive” or “negative” to help distinguish epithelial ovarian cancers from other tumors (Al-Hussaini et al, 2004). WT1 is a particularly sensitive and specific marker for serous ovarian cancer (Acs et al, 2004). Ovarian tissue microarrays at MSKCC (New York, USA) suggest approximately 80% of serous ovarian cancers express WT1 (Lim et al, 2016), thus corroborating earlier studies with IHC (Tornos et al, 2005; Köbel et al, 2009; Karamurzin et al, 2013). Overexpression of the PD-1 ligand PD-L1 has been demonstrated in OvC and may hinder an effective antitumor immune response (http://abstracts.asco.org/199/AbstView_199_184843.html). The activity of anti-PD1 agents in recurrent OvC in second and third lines of therapy is reflected in ORR values of approximately 15% (Varga et al, 2015; Weiss et al, 2017). In a previous clinical study with pembrolizumab with 15.5 months of follow-up, as well as in a review of the existing recent literature in the use of PD-1 blockers in OvC, pembrolizumab continued to be well tolerated and demonstrated durable antitumor activity in patients with advanced OvC (Mittica et al, 2016). In view of the above, there is good rationale to investigate the combination of galinpepimut-S plus pembrolizumab in OvC. 1.3.1.2.3 . Small Cell Lung Cancer (Second Line) Treatment options for patients with SCLC who progress on platinum-based chemotherapy are limited. WT1 expression has not been studied in SCLC as extensively as in NSCLC, mainly due to the relative rarity of the former. Nonetheless, WT1 positivity is higher (40 to 83%) in SCLC versus NSCLC (Babiak et al, 2014; Menssen et al, 2000; Oji et al, 2002; SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 102 Wang et al, 2013). Therefore, WT1 is an appropriate target for direct TAA -specific immunotherapy approaches, such as galinpepimut-S. Pembrolizumab, an anti–PD-1 monoclonal antibody designed to block the interaction between PD -1 and its ligands PD-L1 and PD-L2, has shown antitumor activity in multiple advanced malignancies, including thoracic tumors such as NSCLC and SCLC (http://meetinglibrary.asco.org/record/109650/abstract) . The median PFS and OS following initial chemotherapy in extensive stage small cell lung cancer (ES-SCLC) patients are 2 and 7 months, respectively (Ready, 2015). Maintenance therapy with pembrolizumab did not improve PFS in these patients but favorable OS suggests that some SCLC patients can benefit from maintenance pembro lizumab (Clinical trial information: NCT02359019; http://abstracts.asco.org/199/AbstView_199_183991.html). In patients with PD-L1+ SCLC who have progressed on prior platinum-based therapy, pembrolizumab is generally well tolerated and has promising antitumor activity. Enrollment in the SCLC cohort of KEYNOTE-028 is ongoing (Clinical trial information: NCT02054806). The activity of anti-PD1 agents in SCLC in the second line of therapy is reflected in ORR values of about 33 to 37% (Ott et al, 2016; Hellman et al, 2016; Antonia et al, 2016; Riess et al, 2016). In view of the above, there is good rationale to investiga te the combination of galinpepimut-S plus pembrolizumab in SCLC. 1.3.1.2.4. Breast Cancer (Triple Negative; Second Line) While many histologic/genetic variants of breast cancer have effective treatments, to date, treatments for TNBC have been minimally effective (Bianchini et al, 2016). Although WT1 expression occurs in 70 to 80% of patients with basal-type breast cancer, in specimens from TNBC (Provenzano et al, 2016; Domfeh et al, 2008), WT1 expression is approximately 8 to 15%. Nonetheless, this value may represent low sensitivity of currently used, commercially available anti-WT1 monoclonal antibodies used for IHC (Ichinohasama, 2010). Additionally, WT1 has been found to be focally amplified in a significant proportion of TNBC’s and hence is still a valid immuno-oncology target, despite its low abundance observed ( Craig et al, SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 103 2012). Hence, galinpepimut-S could in principle be active in a significant proportion of TNBC patients. Current anti-PD1 therapies have shown modest monotherapy activity in recu rrent TNBC (second line), as reflected in ORR values of approximately 18% ( Nanda et al, 2016; Hartkopf et al, 2016; Migali et al, 2016; Emens et al, 2015; Dirix et al, 2018; Adams et al, 2016; Emens et al, 2016; Dua and Tan 2017). In view of the above, there is good rationale to investigate the combination of galinpepimut-S plus pembrolizumab in TNBC. 1.3.1.2.5. Acute Myelogenous Leukemia (AML) AML, a clonal, neoplastic, hematopoietic disorder, is the predominant form of acute leukemia in adults. It has an incidence of approximately 2.5 per 100,000 persons and this incidence increases with age, with approximately half of patients with newly diagn osed AML older than 65 years. While most patients are able to achieve CR using anthracycline/cytarabine-based chemotherapy, the benefit associated with standard intensive chemotherapy remains debated in older patients , as well as those with medical co-morbidities because of excessive toxicity and short response duration. Response rates to conventional induction chemotherapy regimens in older patients are around 50%; and median survival is usually less than 1 year (Appelbaum et al, 2006; Döhner Het al, 2015). Despite recent advances in targeted therapy in certain subgroups of AML patients with predefined molecular aberrations (such as FLT3 internal tandem duplication [ITD], isocitric dehydrogenase 1 [IDH1] mutations, and CD33 expression; summarized in Wei and Tiong, 2017 and Stahl et al, 2017) and the advent of a liposomally delivered chemotherapy formulation as well as potential future cell-based immunotherapies (Bose P et al, 2017; Sallman and Lancet, 2017; Short and Ravandi, 2016; De Kouchkovsky and Abdul-Hay , 2016; Dombret and Gardin, 2016; Gbolahan et al, 2017), the tolerability of long term/ full-dose administration of such agents in the same subgroup of patients (those ≥ 60 years of age and/or those with comorbidities) will probably remain a challen ge. The DNA methyltransferase inhibitors, azacitidine and decitabine are currently extensively used in this type of patients, because of their relatively mild side effects ( Kaminskas et al, 2005). Both drugs have a complex SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 104 mechanism of action (MOA) involving epigenetic modification of entire groups of genes, thus leading to marked effects on the pattern of gene expression post - therapy (Cruijsen et al, 2014). These 2 drugs are also called hypomethylating agents (HMAs); some of their effects are pro-differentiating, while others lead to cell killing of leukemic blasts, especially those AML blasts with unfavorable cytogenetic characteristics (Maurillo, 2012). Recent Phase 3 trials have shown the superiority of HMAs when compared with conventional care for older AML patients (not eligible for intensive treatment). HMAs are FDA-approved and widely used as frontline AML therapy for long -term disease control in patients unable to have an allogeneic (allo -) hematopoietic stem cell transplant (HSCT) or as a promising strategy to “bridge” allo-HSCT-candidate patients to the potential curative treatment of a transplant (Gbolahan et al, 2017; Ustun et al, 2013). The above notwithstanding, achievement of CR rates with HMAs in AML remains rather low, ranging from 8% to 32% depending on the series. (Gardin and Dombret 2017; Thomas and Le Jeune, 2017; Yun et al, 2008; Feldman, 2016). Another 10 to 20% of AML patients reach partial response (PR), whereas, up to 45 to 50% of patients do not respond to HMAs with either PR or CR (Sekeres, 2013). The prognosis of patients who achieve less than CR after at least 4 cycles of HMA therapy is worse than those able to achieve CR (after 4 cycles), although PR can be relatively prolonged in select cases. Of note, HMA interruption should be avoided once a sustained response, including PR, has been achieved. With regard to patients who continue on HMAs once they reach PR after the first 4 cycles , most prove unable to convert this PR into a CR (Müller and Florek, 2014; Malik and Cashen, 2014). Hence, the probabilty of such a conversion (i.e,, achievement of CR) in this subpopulation with continuation of HMAs alone after the fourth cycle is probably <5% (Cashen et al, 2010; Joeckel and Lübbert, 2012; Park et al, 2017). WT1 is strongly and prevalently (90 to 95% of cases) expressed in AML blasts both in the peripheral blood (PB) and BM (Inoue et al, 1998; Hosen et al, 2002; Keilholz et al, 2005; Cilloni et al, 2009; Menssen et al, 1995; Inoue et al, 1997). It is also expressed in leukemic stem cells (LSCs) (Saito et al, 1997; Yong et al, 2008). WT1 expression is reliable enough to SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 105 be used as a marker of MRD in AML (as a molecular marker of relapse/response) ( Alonso- Dominguez et al, 2012; Messina et al, 2014; Ogawa et al, 2003; Candoni et al, 2009; Hämäläinen et al, 2008; Mulé et al, 2016) and is typically included in MRD diagnostic multi- gene panels (Buccisano et al, 2017). As noted above, galinpepimut-S has shown activity (as assessed by median PFS and median OS since the time of initial diagnosis versus historical controls) in AML patients who were able to achieve their CR1 after standard induction chemotherapy, as well as 1 to 4 post-CR1 cycles of administration of further ‘consolidation’ chemotherapeutic regimen, after the completion of which they received galinpepimut-S as ‘consolidation’ chemotherapeutic regimen, after the completion of which they received galinpepimut-S as ‘maintenance’ (Maslak et al, 2007; Maslak et al, 2010; Maslak et al, 2018; SELLAS, Data on file). There is theoretical rationale for cytocidal activity by CTLs after galinpepimut-S against LSCs as well, which are especially resistant to either chemotherapy or HMAs (McCracken et al, 2016; Lane et al, 2009; Krause and Scadden, 2015). Consequently, direct WT1-specific immunization with galinpepimut-S in the context of partially controlled disease (AML achieving PR, but not CR, while on HMAs) could principally convert some of these PRs into CRs. With regard to activity of checkpoint inhibitors in AML, to date, anti -PD1 therapies have shown modest activity in relapsed AML (second line) when given after HMAs (Lichtenegger et al, 2017; Haroun et al, 2017). However, PD1 blockers administered in combination with HMAs were shown to be associated with ORR values of up to 34% (Daver et al, 2016; Daver et al, 2017; Nagler et al, 2017; Krupka et al, 2016; Sehgal et al, 2015; http://www.targetedonc.com/publications/targeted -therapies- cancer/2017/2017- february/immune-checkpoint-approaches-in-aml-and-mds-a-next-frontier). Thus, it is very likely that a minority of patients who are unable to respond to HMA monotherapy any deeper than PR may convert their response to CR after receiving concomitant ther apy with checkpoint inhibitors. The exact frequency (rate) of achievement of CR post-combination therapy in such patients remains ill defined, but is probably not exceeding 15% (approximately 50% of the ORR of 30-34% seen in studies by Daver’s group at the MD Anderson Cancer Center (Daver et al, 2016; Daver et al, 2017; Boddu et al, 2018). Finally, SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 106 there is recent evidence suggesting that HMA therapy upregulates PD1 expression in the TME-infiltrated BM of AML patients as well as MHC class I molecules in blasts, thus providing cogent molecular targets for an effect of PD1 inhibition (Ørskov et al, 2015) and galinpepimut-S action, respectively. In view of the above, there is good rationale to investigate the combination of galinpepimut-S plus pembrolizumab in AML patients who cannot achieve responses deeper than PR while having been exposed to at least 4 cycles of HMAs given for first-line/upfront therapy. SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 107 2 Study Objectives 2.1 Primary Objective Hypothesis #1: Combining galinpepimut-S with pembrolizumab could increase the clinical benefit of pembrolizumab monotherapy ( Seledstov et al, 2015; Kleponis et al, 2015) as assessed by improved ORR values versus historical controls for each individual tumor type tested. This would constitute a “positive efficacy signal” (as relevant to a particular tumor type) and warrant broader future clinical investigations. Further, the combination will not increase the burden of toxicities and will have an overall similar/comparable AE profile as pembrolizumab monotherapy. Based on the above hypothesis, the primary objectives of the study are: • To evaluate the safety and tolerability of galinpepimut -S in combination with pembrolizumab in patients with selected advanced cancers • To evaluate the anti-tumor activity of the combination of galinpepimut-S and pembrolizumab as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 to determine if the activity seen is sufficiently promising to evaluate the combination in future clinical studies. For AML patients: to study the possibility of achieving morphologic CR (including CR with incomplete recovery of blood counts or platelets [CRi/CRp]), i.e., conversion of morphologic PR into CR/CRi/CRp. Included are the following cohorts: o Patients with metastatic CRC previously treated with at least 2 lines of prior systemic chemotherapy (third/fourth line population) (n = 20). o Patients with metastatic OvC second/third line population (n = 20) o Patients with advanced SCLC previously treated with 1 line of prior system ic chemotherapy (second line population) (n = 20) SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 108 o Patients with TNBC previously treated with 1 line of prior systemic chemotherapy (second line population) (n = 15) o Patients with AML (any age) who are not eligible for allogeneic hematopoietic stem cell transplant (allo-SCT) and have only been able to achieve PR while receiving frontline therapy with HMAs (n = 15) 2.2 Secondary Objective s The secondary objectives of this study are: • To evaluate the clinical benefit of galinpepimut-S in combination with pembrolizumab in patients with selected advanced cancers through the analysis of time to response (TTR), time to next treatment, and duration of response (DOR). 2.3 Exploratory Objectives Hypothesis #2: Combining galinpepimut-S with pembrolizumab could lead to the development of a robust WT1-specific immune response against patients’ cancers, and potentially improve the abundance and functionality of the hosts’ immunocytes within the TME (versus pembrolizumab monotherapy) (Duraiswamy et al, 2013). Positive correlative analyses (as relevant to a particular tumor type) between immune and clinical outcomes would provide a MOA framework to inform the design of future larger, randomized clinica l studies in that tumor type. Based on the above hypothesis, the exploratory objectives of this study are: SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 109 • To assess ORR per immune RECIST (iRECIST) in patients in the solid tumor arms • To assess the frequency (rate) of achievement of MRD negativity in patients in the AML arm • To further characterize the immunodynamics profile of galinpepimut-S and pembrolizumab combination therapy through analyses of WT1-specific CD8 and CD4 cells in PB, as well as WT1-specific memory CD8 T cells, MDSC, and T-regulatory cells [Treg] in PB • To gauge the general immunodynamics effects upon non -antigen-specific lymphocyte immunophenotypic subtypes will be studied in PB via flow cytometry • To assess the effects of the combination on defined biomarkers of immune checkpoint activity in the tumors (or bone marrow for AML patients) and their surrounding microenvironment (pharmacodynamics specific to pembrolizumab) • To assess the association between selected biomarker readouts and clinical efficacy measures at specific time-points, using pre-treatment and on-treatment tumor biopsies • To assess OS and PFS SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 110 3 Investigational Plan 3.1 Study Design This is a Phase 1/2, open-label, non-comparative, multicenter, multi -arm study of the combination of galinpepimut-S in combination with pembrolizumab in patients with selected advanced cancers. This study will assess the efficacy and safety of galinpepimut-S and pembrolizumab and investigate the effect of galinpepimut -S and pembrolizumab on various tumor types. Patients will be followed long-term for OS and safety. The study will enroll approximately 90 patients. Sites will primarily be major tertiary academic oncology centers and will be selected based on expertise in complicated dosing scenarios . WT1 IHC staining characteristics for all tumor/BM samples will be assessed by central pathology review (to be performed by senior pathologists who will undergo study-specific training). 3.1.1. Overall Treatment Investigational Administration Schedule Patients will receive 70 μg sargramostim (GM-CSF) SC on Day -2 and on Day 1 before each galinpepimut-S injection. The first GM-CSF injection of each doublet will occur at the same anatomical site of the planned galinpepimut -S treatment injection within each given cycle. The first 2 galinpepimut-S injections will initially be administered as monotherapy every 3 weeks (Week 0 and Week 3). Thereafter, galinpepimut-S will be co-administered with pembrolizumab every 3 weeks for 4 additional administrations (for the galinpepimut -S initial immunization induction phase series; weeks 6-15) to coincide with the per label pembrolizumab dosing frequency. After that, there will be one un -paired administration of pembrolizumab (week 18), and then galinpepimut-S will be resumed on an every 3-week schedule for 6 additional doses (early immune booster phase; weeks 21 -36). At the end of this phase, there will be a 12-week interval where 3 unpaired administrations of SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 111 pembrolizumab will occur (weeks 39-45), and then galinpepimut-S will be resumed on an every 12-week schedule for 4 additional doses (late immune booster phase; weeks 48 -84). After 84 weeks, continuing non-progressed patients will be treated with pembrolizumab alone up until week 111. Galinpepimut-S will be administered 30-60 minutes after the completion of IV infusion of pembrolizumab on Day 1 of each cycle during which the 2 drugs are being co-administered. Pembrolizumab will be administered at a dose of 200 mg intravenously every 3 weeks on Day 1 of each cycle (3-week cycles) starting on Study Week 6 and continuing for up to 2 years thereafter (Study Week 111). To monitor for any adverse reactions, specifically for systemic anaphylaxis type reactions against either GM -CSF or galinpepimut-S, patients will remain in the clinic for approximately 30 minutes following each GM-CSF or galinpepimut- S injection. Safety assessments will be conducted at every visit. The end of treatment (EOT) visit will occur 30 days after the last injection. Specifically for patients in the AML arm, the timing of the administration o f the investigational therapies (pembrolizumab and galinpepimut -S) with respect to administration of hypomethylating agents (HMAs) will be as follows: • AML patients on cycles #1 – 4 of HMA on-label therapy (treated according to standard clinical care) will be pre-screened to gauge potentially eligibility for the study. • If restaging bone marrow biopsy immediately after the completion of cycle #4 of HMA therapy demonstrates morphological partial response (PR), then such patients become eligible for the study and can initiate investigational therapy (pembrolizumab and galinpepimut-S), as long as the latter commences prior to the initiation of cycle #5 of the HMA. • Reasonable efforts will be made by the Contracted Research Organization (CRO), Cancer Insight, LLC, at actively enrolling clinical sites to initiate investigational therapy within 14 +/7 days from the completion of cycle #4 of HMA therapy, to ensure relative homogeneity in the initiation timing relationship between the two SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 112 therapeutic modalities, i.e., HMA and investigational therapy. Furthermore, for clarification purposes, each cycle of therapy in patients in the AML arm will be defined by the frequency of administration of the study investigational agents (pembrolizumab and galinpepimut- S), i.e., 3 weeks. This clarification is important, because: a. patients in the AML arm will continue their HMA therapy throughout the administration of study investigational agents and b. the timing of initiation between HMA cycle #5 and that of the first administra tion of investigational therapies are de-linked. The study design is shown in SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 113 Figure 12 and the overall treatment schedule is provided in Figure 13. The study endpoints are defined in Section 7. SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 114 Figure 12 Study Design 3.1.2. Rationale of Study Design There is clearly an unmet need for novel and effective therapy to improve responses and prolong disease remission/progression-free intervals already achieved with checkpoint blockade monotherapy (Farkona et al, 2016). The objectives of this proposed clinical study SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 115 are: (i). to explore clinical outcomes (safety and potentially promising activity) in tumors using a combination of agents that improve immune-mediated anticancer effects, namely, pembrolizumab and galinpepimut-S, and (ii). to maximize the chances of detecting a clinically meaningful efficacy signal in comparison to historical monotherapy data (with pembrolizumab alone) for further validation in larger, randomized trials. To meet these objectives, the current design of a Phase 1/2 open -label, non-comparative, multicenter, multi-arm clinical study was chosen, as it has been used successfully in similar studies beforehand (Menis et al, 2014; Toulmonde et al, 2018; Goldberg et al, 2016), and therefore considered as highly suitable for this trial . SELLAS Life Sciences Group Galinpepimut -S Protocol : SLS17 -201/MK3475 -770 Protocol v1.1 (Amendment 1.0) 12 April 2019 Page 116 4.0. Patient Selection and Withdrawal Criteria 4.1. Selection of Study Population Patients will be enrolled into the study only if they meet all of the inclusion criteria and none of the exclusion criteria. Deviations from the inclusion and exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity o f the study, regulatory acceptability, or patient safety. Therefore, adherence to the criteria as specified in the protocol is essential . Patients who do not initially meet all of the inclusion criteria and none of the exclusion criteria may be allowed to retest for laboratory evaluations and other procedures within 28 days of signing the informed consent form (ICF) without being considered a rescreen. If the patient then meets all inclusion/exclusion criteria, they are permitted to be enrolled into the study. If a patient does not meet inclusion/exclusion criteria within the 28 days of signing the ICF, the patient will be considered a screen failure and may be allowed to re -screen with a newly signed ICF up to 2 times. 4.1.1. Inclusion Criteria Each patient must meet all of the following criteria to be enrolled in this study: Type of Participant and Disease Characteristics 1. Is willing and able to understand and provide signed informed consent for the study that fulfills Institutional Review Board (IRB) guidelines 2. Male or female patients ³ 18 years of age on the day of signing informed consent.