A Study of the Efficacy and Safety of Galinpepimut-S (GPS) for the Treatment of Acute Myeloid Leukemia Compared to Investigator's Choice of Best Available Therapy

Prior treatment

• 1- For subjects randomized to GPS maintenance monotherapy: a. Continuation of any agents administered as part of induction of CR2/CRp2 or later b. Receiving any concurrent anti-AML systemic therapy c. Prior clinically significant allergic reaction to Montanide, sargramostim (GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]). d. Received any consolidation and/or maintenance antileukemic therapy, investigational agent, systemic corticosteroid therapy, or other immunosuppressive therapy within 4 weeks prior or 10 half lives, whichever is shorter prior to receiving study treatment. Systemic corticosteroids for chronic conditions (at doses ≤ 10 mg/day of prednisone or equivalent) are permitted, as are inhalational, intra-ocular, intra-articular and topical corticosteroids as well as any corticosteroids or other immunosuppressive therapies that do not act systemically (e.g. budesonide) at any dose level.
• 8- Pat who had an SCT after their most recent re-induction that resulted in CR2 or CRp2 or later are not eligible. Pat. with prior SCT are allowed only if they had SCT prior to their latest re-induction or achieved CR by means of transplant.
• 9- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of systemic immunosuppressive therapy exceeding 10 mg daily of prednisone equivalent within 7 days prior the first dose of study drug. The use of physiologic doses of corticosteroids and/or immunosuppressive agents may be approved after consultation with the Sponsor. Steroids taken as short-term therapy (≤ 7 days) for antiemesis are permissible.
• 13-Had a previous clinically significant systemic allergic reaction to Montanide, sargramostim (GM-CSF), or filgrastim (G-CSF)
• 19-Has had an allogeneic tissue/solid organ transplant.
• 11- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• 2- Subjects with an imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor).
• 4- Subjects with a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in the clinical study.
• 6- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Vaccines for Covid-19 used under an EUA, are considered an authorized (though not an approved or cleared) medical product for use in clinical care. Vaccines used for the prevention of Covid-19 are allowed to be used.
• 7- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks, or in the case of drugs 10 half lives, whichever is shorter, prior to the first dose of study treatment.

Other illness

• 12-Has known hypersensitivity to Montanide or vaccine adjuvants.
• 14-Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy is not considered a form of systemic treatment and is allowed.
• 15-Has an active life threatening infection requiring systemic therapy.
• 17-Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
• 10- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years, even if currently inactive or unapparent.

Lab values

• 16-Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Other

• 18-Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 30 days after the last dose of study treatment.
• 3- Subjects with acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
• 5- Subjects who currently have, central nervous system leukemia

• Patients, or their legally acceptable representatives, must be willing and able to understand and provide signed informed consent for the study that fulfills Institution Review Board (IRB) guidelines.
• Subjects must have an estimated life expectancy >6 months.
• If female, is postmenopausal (at least 12 sequential months of amenorrhea) or surgically sterile. Females of childbearing potential must have a negative pregnancy test.
• Female patients of childbearing potential who are heterosexually active and male patients with female sexual partners of childbearing potential must agree to use an effective method of contraception (e.g., oral contraceptives, double-barrier methods such as a condom and a diaphragm, intrauterine device) during the study and for 4 to 6 months (depending on treatment) following the last dose of study medication, or to abstain from sexual intercourse for this time; a woman not of childbearing potential is one who has undergone bilateral oophorectomies or who is post- menopausal, defined as the absence of menstrual periods for 12 consecutive months.
• Subjects must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1 after completion of prior AML therapy with the exception of the platelet count requirements (i.e., as long as peripheral blood platelet count is >20,000/µL).
• Subjects must not have end stage renal disease.
• Subjects must have adequate hepatic function defined as a serum total bilirubin as a serum total bilirubin <2 x ULN (except for Gilbert’s syndrome, which will allow bilirubin ≤3.0 mg/dL and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN.
• Subjects must be willing and able to return to the clinical site for adequate follow-up and to comply with the protocol as required
• Male or female patients > 18 years of age on the day of signing informed consent.
• Subjects must have a diagnosis of AML according to the WHO criteria (primary/de novo or secondary, including treatment-related [e.g., due to prior anthracycline use], as well as cases due to progression of antecedent hematological disorder [e.g., MDS, MPN, or MDS/MPN 'overlap' syndrome).
• Les patients doivent être en deuxième rémission morphologique complète ou ultérieure (avec ou sans récupération des plaquettes ; RC2/RCp2) pour une LMA en rechute, selon les critères de RCp suivants : a. < 5 % de myéloblastes dans la moelle osseuse. b. Absence de corps d'Auer. c. Absence de blastes périphériques circulants. d. Nombre absolu de neutrophiles (NAN) du sang périphérique >1000 cellules/µL. e. Numération plaquettaire du sang périphérique >20 000/µL. f. Absence de maladie extra-médullaire.
• Patients must have > 300 lymphocytes/ µL.
• Subjects must not be candidates at the time of study entry for allogeneic stem cell transplant (Allo-SCT) due to intercurrent medical conditions, patients preference or lack of an available donor.
• Subjects must have received the last dose of re-induction antileukemic therapy at least 4 weeks or ten half-lives of induction chemotherapy (whichever is shorter) prior to receiving study treatment.
• Subjects must be consented within 6 months of having achieved CR2/CRp2 or later.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1,2 or 3.