Clinical Trials /

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

NCT03761914

Description:

To evaluate the safety and tolerability of galinpepimut-S in combination with pembrolizumab in patients with selected advanced cancers. Patients will be followed long-term for Overall Survival (OS) and safety. The study will enroll approximately 90 patients and maximum study treatment duration is approximately 2.13 years.

Related Conditions:
  • Acute Myeloid Leukemia
  • Breast Carcinoma
  • Colorectal Adenocarcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Galinpepimut-S in Combination With Pembrolizumab in Patients With Selected Advanced Cancers
  • Official Title: A Phase 1/2 Study of Galinpepimut-S in Combination With Pembrolizumab (MK 3475) in Patients With Selected Advanced Cancers

Clinical Trial IDs

  • ORG STUDY ID: SLS17-201/MK3475-770
  • NCT ID: NCT03761914

Conditions

  • Acute Myelogenous Leukemia
  • Ovarian Cancer
  • Colorectal Cancer
  • Triple-negative Breast Cancer
  • Small-cell Lung Cancer

Interventions

DrugSynonymsArms
galinpepimut-SSLS-001, GPS, WT1 Analog Peptide VaccineColorectal Cancer (CRC)
PembrolizumabMK-3475, KeytrudaColorectal Cancer (CRC)

Purpose

To evaluate the safety and tolerability of galinpepimut-S in combination with pembrolizumab in patients with selected advanced cancers. Patients will be followed long-term for OS and safety. The study will enroll approximately 90 patients and maximum study treatment duration is approximately 2.13 years.

Detailed Description

      This is a Phase 1/2, open-label, non-comparative, multicenter, multi-arm study of the Wilms
      Tumor-1 (WT1)-targeting multivalent heteroclitic peptide immunotherapeutic vaccine
      galinpepimut-S in combination with the programmed death-1 (PD1) inhibitor 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 at up to 20 centers in the United States.

      Indications treated are colorectal (third or fourth line), ovarian (second or third line),
      small cell lung cancer (second line), breast cancer (triple negative; second line), acute
      myelogenous leukemia (unable to attain deeper morphological response than partial [PR] on
      hypomethylating agents and who are not eligible for allogeneic hematopoietic stem cell
      transplant).

      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 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.

      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). Pembrolizumab will be administered no earlier than 30 minutes
      after the administration of galinpepimut-S on Day 1 of each cycle where the 2 drugs are being
      co-administered.
    

Trial Arms

NameTypeDescriptionInterventions
Colorectal Cancer (CRC)ExperimentalN=20; Subjects with metastatic CRC previously treated with ≥2 lines of prior systemic chemotherapy (3rd/4th line population); PFS and OS to be assessed in all; Patients will receive GM-CSF before each galinpepimut-S vaccine injection. The first 2 vaccine injections will be administered as monotherapy every 3 weeks. Thereafter, the vaccine will be co-administered with pembrolizumab every 3 weeks for another 4 administrations. After that, there will be one unpaired administration of pembrolizumab, and then the vaccine will be resumed on an every 3-week schedule for 6 additional doses. At the end of this phase, there will be a 12-week interval where 3 unpaired administrations of pembrolizumab will occur, and then the vaccine will be resumed every 12 weeks for an additional 4 doses. After 84 weeks, patients who have not progressed will continue in the study and will be treated with pembrolizumab alone.
  • galinpepimut-S
  • Pembrolizumab
Ovarian Cancer (OvC)ExperimentalN=20; Patients with metastatic OvC previously treated with ≥1 line of prior systemic chemotherapy (2nd/3rd line population); PFS and OS to be assessed in all; Patients will receive GM-CSF before each galinpepimut-S vaccine injection. The first 2 vaccine injections will be administered as monotherapy every 3 weeks. Thereafter, the vaccine will be co-administered with pembrolizumab every 3 weeks for another 4 administrations. After that, there will be one unpaired administration of pembrolizumab, and then the vaccine will be resumed on an every 3-week schedule for 6 additional doses. At the end of this phase, there will be a 12-week interval where 3 unpaired administrations of pembrolizumab will occur, and then the vaccine will be resumed every 12 weeks for an additional 4 doses. After 84 weeks, patients who have not progressed will continue in the study and will be treated with pembrolizumab alone.
  • galinpepimut-S
  • Pembrolizumab
Small Cell Lung Cancer (SCLC)ExperimentalN=20; This arm includes patients with advanced SCLC previously treated with 1 line of prior systemic chemotherapy (2nd line population); PFS and OS to be assessed in all; Patients will receive GM-CSF before each galinpepimut-S vaccine injection. The first 2 vaccine injections will be administered as monotherapy every 3 weeks. Thereafter, the vaccine will be co-administered with pembrolizumab every 3 weeks for another 4 administrations. After that, there will be one unpaired administration of pembrolizumab, and then the vaccine will be resumed on an every 3-week schedule for 6 additional doses. At the end of this phase, there will be a 12-week interval where 3 unpaired administrations of pembrolizumab will occur, and then the vaccine will be resumed every 12 weeks for an additional 4 doses. After 84 weeks, patients who have not progressed will continue in the study and will be treated with pembrolizumab alone.
  • galinpepimut-S
  • Pembrolizumab
Triple Negative Breast Cancer (TNBC)ExperimentalN=15; Patients with TNBC previously treated with 1 line of prior systemic chemotherapy (2nd line population); PFS and OS to be assessed in all; Patients will receive GM-CSF before each galinpepimut-S vaccine injection. The first 2 vaccine injections will be administered as monotherapy every 3 weeks. Thereafter, the vaccine will be co-administered with pembrolizumab every 3 weeks for another 4 administrations. After that, there will be one unpaired administration of pembrolizumab, and then the vaccine will be resumed on an every 3-week schedule for 6 additional doses. At the end of this phase, there will be a 12-week interval where 3 unpaired administrations of pembrolizumab will occur, and then the vaccine will be resumed every 12 weeks for an additional 4 doses. After 84 weeks, patients who have not progressed will continue in the study and will be treated with pembrolizumab alone.
  • galinpepimut-S
  • Pembrolizumab
Acute Myelogenous Leukemia (AML)ExperimentalN=15; Pts with AML who are not eligible for allogeneic stem cell transplant and have only been able to achieve morphological PR while receiving frontline therapy with HMAs; PFS and OS to be assessed in all; Patients will receive GM-CSF before each galinpepimut-S vaccine injection. The first 2 vaccine injections will be administered as monotherapy every 3 weeks. Thereafter, the vaccine will be co-administered with pembrolizumab every 3 weeks for another 4 administrations. After that, there will be one unpaired administration of pembrolizumab, and then the vaccine will be resumed on an every 3-week schedule for 6 additional doses. At the end of this phase, there will be a 12-week interval where 3 unpaired administrations of pembrolizumab will occur, and then the vaccine will be resumed every 12 weeks for an additional 4 doses. After 84 weeks, patients who have not progressed will continue in the study and will be treated with pembrolizumab alone.
  • galinpepimut-S
  • Pembrolizumab

Eligibility Criteria

        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

          -  Has 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 will be tested for WT1 expression via IHC in both their initial primary
             tumor and recent biopsy of metastatic disease at the time of screening for study
             entry, or, specifically for AML, leukemic blasts either in the BM or PB.

          -  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)

          -  Have measurable disease based on RECIST v1.1 as determined by the local study team.

          -  AML patients are allowed to have undergone prior chemotherapy (other than HMAs), but
             should have received the last dose of their most recent chemotherapy regimen at least
             28 days prior to first galinpepimut-S administration.

          -  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)≥1,500 /mcL

               -  Platelets ≥100,000 / mcL

               -  Hemoglobina ≥ 9 g/dL or ≥5.6 mmol/L,

               -  Renal Creatinine OR Measured or calculated creatinine clearance ≤ 1.5 ULN OR ≥ 30
                  mL/min for patient with creatinine levels >1.5 institutional ULN

               -  Total bilirubin ≤1.5 ULN OR direct bilirubin ≤ULN for patients with total
                  bilirubin levels >1.5ULN.

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5ULN OR ≤ 5ULN for patients with liver metastases

               -  INR or PT/PTT ≤1.5 ULN unless patient is receiving anticoagulant therapy as long
                  as PT or PTT is within therapeutic range of intended use of anticoagulants

        Additional Inclusion Criteria for Selected Tumor Types:

        (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).

        (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.

          -  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.

             (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 shall remain on HMA therapy.

        Exclusion Criteria:

          -  Has disease that is suitable for local therapy administered with curative intent.

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first study treatment.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10mg daily of prednisone equivalentor a maximum dose of a
             corticosteroid not to exceed 10 mg). Steroids taken as short-term therapy (≤7 days)
             for antiemesis are permissible.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to first
             study treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due
             to agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 3 months prior to first study treatment or who has not recovered (i.e., ≤ Grade
             1 or at baseline) from AEs due to a previously administered agent.

        Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this
        criterion and may qualify for the study.

        Note: If patient received major surgery, they must have recovered adequately from the
        toxicity and/or complications from the intervention prior to starting study drugs.

          -  Has received transfusion of blood products (including platelets or red blood cells) or
             administration of colony stimulating factors (excluding GM-CSF, but including G-CSF or
             recombinant erythropoietin) within 4 weeks prior to first study treatment.

          -  Has a known additional malignancy that is progressing or requires active treatment.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Note: Patients with previously treated brain metastases and/or
             carcinomatous meningitis may participate provided they are clinically stable for at
             least 2 weeks and, have no evidence of new or enlarging brain metastases, AND are also
             off steroids 3 days prior to first study treatment. Subjects with known untreated,
             asymptomatic brain metastases (ie, no neurological symptoms, no requirements for
             corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may
             participate but will require regular imaging of the brain as a site of disease.

          -  Active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
             drugs) or history of an autoimmune disease that required immune suppressive therapy,
             such as but not limited to inflammatory bowel disease, systemic lupus erythematosus,
             ankylosing spondylitis, scleroderma, or multiple sclerosis. History of vitiligo is
             permissible. Replacement therapy (e.g., thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

          -  Has a history of interstitial lung disease(ILD).

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the patient's
             participation for the full duration of the trial, or is not in the best interest of
             the patient to participate, in the opinion of the treating investigator. This includes
             any serious, intercurrent, chronic, or acute illness, such as cardiac disease (New
             York Heart Association [NYHA] class III or IV), hepatic disease, or other illness
             considered by the investigator as an unwarranted high risk for investigational drug
             treatment.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial or judged by the treating investigator
             that such disorders could possibly lead to noncompliance with the protocol.

          -  A WOCBP who has a positive urine pregnancy test (e.g., within 72 hours prior to
             treatment). If the urine test is positive or cannot be confirmed as negative, a serum
             pregnancy test will be required.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA
             4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher
             irAE.

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

          -  Has known active hepatitis B (e.g., hepatitis B antigen [HBsAg] reactive) or hepatitis
             C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected).

          -  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.

          -  Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.

          -  Has known hypersensitivity to Montanide or vaccine adjuvants.

          -  Had a previous clinically significant systemic allergic reaction to Montanide,
             sargramostim (GM-CSF), or filgrastim (G-CSF).

        Additional Exclusion Criteria for Selected Tumor Types:

        (i). CRC: None (ii). OvC: None (iii). SCLC: Mixed SCLC (iv). TNBC: None (v). AML:

          1. Planned/anticipated HSCT (autologous or allogeneic, with any degree of match donor);
             acute promyelocytic leukemia (APL; M3 or any morphologic and molecular variants,
             inclusive); history of, or current diagnosis of CNS leukemia

          2. Second line patients or patients who received any chemotherapy ("3 + 7" regimen) and
             subsequently switch to HMAs are ineligible for enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Number and frequency of TRAEs, including UARs, and SAEs (safety parameters) - for all tumor types
Time Frame:First 9 weeks up to 32 months
Safety Issue:
Description:Define the absolute number, relative frequency, and severity (grade) of treatment-related adverse events (TRAEs), including unexpected adverse reaction (UARs), as well as serious adverse events (SAEs) -irrespective of relationship to study drug - using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. for all patients on study.

Secondary Outcome Measures

Measure:Time to response (TTR) - for all tumor types
Time Frame:First 9 weeks up to 32 months
Safety Issue:
Description: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).
Measure:Time to next treatment (TNT) - for all tumor types
Time Frame:First 9 weeks up to 32 months
Safety Issue:
Description:Evaluate the clinical benefit of galinpepimut-S in combination with pembrolizumab in patients with selected advanced cancers through the analysis of time to next treatment (TNT).
Measure:Duration of Response (DOR) - for solid tumor arms
Time Frame:First 9 weeks up to 32 months
Safety Issue:
Description:Evaluate the clinical benefit of galinpepimut-S in combination with pembrolizumab in patients with selected advanced solid malignancies through the analysis of duration of response (DOR), based on the interval of time between the documentation of ORR (CR/PR) and documentation of progressive disease (PD).
Measure:Duration of CR - for AML arm only
Time Frame:First 9 weeks up to 32 months
Safety Issue:
Description:Evaluate the clinical benefit of galinpepimut-S in combination with pembrolizumab in patients with AML through the analysis of duration of complete response, based on the interval of time between the documentation of CR and documentation of morphological leukemic relapse/progressive disease (PD).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sellas Life Sciences Group

Trial Keywords

  • peptide vaccine
  • immuno-oncology
  • WT1-expressing tumors
  • galinpepimut-S
  • pembrolizumab
  • PD1 inhibitor
  • checkpoint inhibitor
  • combination immunotherapy
  • heteroclitic
  • multivalent
  • off-the-shelf vaccine
  • HLA allele

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