Clinical Trials /

AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT04019288

Description:

This trial studies the side effects and best dose of AVB-S6-500 when given together with durvalumab in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that is resistant to platinum therapy or has come back. Immunotherapy with AVB-S6-500 and durvalumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
  • Official Title: Randomized Phase I/II Study of AVB-S6-500 in Combination With Durvalumab (MEDI4736) in Patients With Platinum-Resistant, Recurrent Epithelial Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2019-0149
  • SECONDARY ID: NCI-2019-02580
  • SECONDARY ID: 2019-0149
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04019288

Conditions

  • Platinum-Resistant Fallopian Tube Carcinoma
  • Platinum-Resistant Ovarian Carcinoma
  • Platinum-Resistant Primary Peritoneal Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Refractory Fallopian Tube Carcinoma
  • Refractory Ovarian Carcinoma
  • Refractory Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
Anti-AXL Fusion Protein AVB-S6-500AVB S6 500, AVB-S6-500, AVBS6500, AXL Fc Fusion Protein AVB-S6-500Arm I (AVB-S6-500, durvalumab)
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Arm I (AVB-S6-500, durvalumab)

Purpose

This trial studies the side effects and best dose of AVB-S6-500 when given together with durvalumab in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that is resistant to platinum therapy or has come back. Immunotherapy with AVB-S6-500 and durvalumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine toxicity profile of the combination of anti-AXL fusion protein AVB-S6-500
      (AVB-S6 -500) and durvalumab therapy.

      SECONDARY OBJECTIVES:

      I. To estimate objective response rate to combination AVB-S6-500 and durvalumab therapy.

      II. To estimate the median immune-related progression free survival (irPFS) as well as
      overall survival (OS) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 after
      treatment with combination durvalumab and AVB-S6-500.

      III. To investigate molecular and immunological changes associated with the combination of
      AVB-S6-500 and durvalumab; specifically to describe changes in T cell populations (including
      but not limited to CD3, CD8, CD4, FOXP3) and cell proliferation, as well as report changes in
      the proportion of macrophage phenotypes M1 and M2 (with phenotypic markers potentially
      including arginase1, CD11b, PDL-1, and CD206).

      EXPLORATORY OBJECTIVES:

      I. To evaluate blood and tissue based biomarkers for immune related adverse events and
      disease progression.

      II. To investigate impact and possible sensitization of pretreatment with AVB-S6-500
      monotherapy on subsequent combination of durvalumab and AVB-S6-500.

      III. To evaluate for molecular and immunologic differences between pre-treatment with single
      agent AVB-S6-500 as compared to durvalumab.

      OUTLINE: This is a phase I, dose-escalation of anti-AXL fusion protein AVB-S6-500, followed
      by a phase II study. In Phase I, patients receive both anti-AXL fusion protein AVB-S6-500
      (intravenously [IV] over 30 minutes on days 1 and 15) and durvalumab (IV over 60 minutes on
      day 1) every cycle.

      In Phase II, patients are randomized to 1 of 2 arms.

      ARM I: Patients receive anti-AXL fusion protein AVB-S6-500 IV over 30 minutes on days 1, 15,
      and 29 of cycle 0, and on days 1 and 15 of subsequent cycles. Beginning cycle 1, patients
      also receive durvalumab IV over 60 minutes on day 1. Cycle 0 continues for 6 weeks and
      subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable
      toxicity.

      ARM II: Patients receive durvalumab IV over 60 minutes on days 1 and 22 of cycle 0 and on day
      1 of subsequent cycles. Beginning cycle 1, patients also receive anti-AXL fusion protein
      AVB-S6-500 IV over 30 minutes on days 1 and 15. Cycle 0 continues for 6 weeks and subsequent
      cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 weeks for at least 90
      days.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (AVB-S6-500, durvalumab)ExperimentalPatients receive anti-AXL fusion protein AVB-S6-500 IV over 30 minutes on days 1, 15, and 29 of cycle 0, and on days 1 and 15 of subsequent cycles. Beginning cycle 1, patients also receive durvalumab IV over 60 minutes on day 1. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Anti-AXL Fusion Protein AVB-S6-500
  • Durvalumab
Arm II (durvalumab, AVB-S6-500)ExperimentalPatients receive durvalumab IV over 60 minutes on days 1 and 22 of cycle 0 and on day 1 of subsequent cycles. Beginning cycle 1, patients also receive anti-AXL fusion protein AVB-S6-500 IV over 30 minutes on days 1 and 15. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Anti-AXL Fusion Protein AVB-S6-500
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to provide signed informed consent

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up

          -  Histology (reviewed at MD Anderson Cancer Center [MDACC]) showing recurrent high grade
             epithelial ovarian, peritoneal, or fallopian tube cancer

          -  Platinum resistant or refractory disease as defined by progression of disease on a
             platinum-containing regimen or recurrence of disease within 180 days of previous
             platinum treatment

          -  Have measurable disease based on modified RECIST 1.1. For the purposes of this study
             measurable disease is defined at least one "target lesion" that can be accurately
             measured in at least one dimension (longest dimension to be recorded). Each target
             lesion must be > 20 mm when measured by conventional techniques, including palpation,
             plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or > 10
             mm when measured by spiral CT. The target lesion must be distinct from other tumor
             areas selected for pre-treatment biopsies. Pre-treatment imaging must be performed
             within 4 weeks of starting therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy of >= 12 weeks

          -  Body weight > 30 kg. Note: if subject's weight falls below 30 kg during study but the
             patient is otherwise eligible to continue investigational therapy the dose of
             durvalumab will be modified to be weight-based (20 mg/kg for the 1500 mg dose;
             modification is not required for 1120 mg dose)

          -  Hemoglobin >= 9.0 g/dL

          -  Absolute neutrophil count (ANC) > 1500/mm^3

          -  Platelet count >= 100 x 10^9/L (> 75,000/mm^3)

          -  Serum bilirubin =< 1.5 x upper limit of normal (ULN)

               -  This will not apply to patients with confirmed Gilbert's syndrome (persistent or
                  recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of
                  hemolysis or hepatic pathology), who will be allowed only in consultation with
                  their physician

          -  Aspartate aminotransferase (AST, serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT, serum glutamic-pyruvic transaminase [SGPT]) =<
             2.5 x ULN unless liver metastases are present, in which case it must be =< 5 x ULN

          -  Measured creatinine clearance (CL) > 40 mL/min or calculated creatinine CL > 40 mL/min
             by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine
             collection for determination of creatinine clearance

          -  Evidence of post-menopausal status or negative serum pregnancy test for female
             pre-menopausal patients. Women will be considered post-menopausal if they have been
             amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women < 50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy)

               -  Women >= 50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses > 1 year ago, had
                  chemotherapy-induced menopause with last menses > 1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy)

          -  Patients must have no currently available standard of care treatment options

        Exclusion Criteria:

          -  Participation in another clinical study with an investigational product (IP) during
             the last 28 days

          -  Concurrent enrollment in another clinical study, unless it is an observational
             (non-interventional) clinical study or during the follow-up period of an
             interventional study

          -  Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine
             therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
             antibodies) =< 28 days prior to the first dose of study drug. If sufficient wash-out
             time has not occurred due to the schedule or pharmacokinetic (PK) properties of an
             agent, a longer wash-out period will be required, as agreed by AstraZeneca, Aravive,
             and the investigator

          -  Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria
             for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
             criteria. Patients with grade >= 2 neuropathy will be evaluated on a case-by-case
             basis after consultation with the study physician. Patients with irreversible toxicity
             not reasonably expected to be exacerbated by treatment with durvalumab may be included
             only after consultation with the study physician

          -  Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment

          -  Major surgical procedure (as defined by the investigator) within 28 days prior to the
             first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
             acceptable

          -  History of allogenic organ transplantation

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
             the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome,
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
             criterion:

               -  Patients with vitiligo or alopecia;

               -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement;

               -  Any chronic skin condition that does not require systemic therapy;

               -  Patients without active disease in the last 5 years may be included but only
                  after consultation with the study physician;

               -  Patients with celiac disease controlled by diet alone

          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirement, substantially increase
             risk of incurring Adverse Events (AEs) or compromise the ability of the patient to
             give written informed consent

          -  Any medical, social, or psychological condition that would interfere with evaluation
             of study treatment or interpretation of patient safety or study results

          -  Active infection including tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and tuberculosis [TB] testing
             in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
             surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
             (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined
             as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
             eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if
             polymerase chain reaction is negative for HCV ribonucleic acid (RNA)

          -  History of another primary malignancy except for the following histories: Malignancy
             treated with curative intent and with no known active disease >= 5 years before the
             first dose of IP and of low potential risk for recurrence; adequately treated
             non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately
             treated carcinoma in situ without evidence of disease

          -  History of leptomeningeal carcinomatosis

          -  Brain metastases or spinal cord compression. Patients with suspected brain metastases
             at screening should have a magnetic resonance imaging (MRI) (preferred) or computed
             tomography (CT), each preferably with intravenous (IV) contrast of the brain prior to
             study entry

          -  Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 470 ms

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of durvalumab or AVB-S6-500. The following are exceptions to this criterion:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
                  articular injection);

               -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
                  prednisone or its equivalent;

               -  Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication)

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
             Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
             90 days after the last dose of IP

          -  Female patients who are pregnant or breastfeeding or of reproductive potential who are
             not willing to employ effective birth control from screening to 180 days after the
             last dose of durvalumab + AVB-S6-500 combination therapy

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients

          -  Unresolved partial or complete small or large bowel obstruction

          -  Judgment by the investigator that the patient is unsuitable to participate in the
             study and the patient is unlikely to comply with study procedures, restrictions and
             requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 1 year
Safety Issue:
Description:Safety will be monitored in the monotherapy phase and in the combination therapy phase. Will tabulate adverse events by grade, and relationship to study drug. Will estimate the proportion of subjects that discontinue treatment due to treatment-related adverse events with 90% confidence intervals. Will estimate the unacceptable toxicity rate with a 90% confidence interval.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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