Clinical Trials /

Intravenous TAEK-VAC-HerBy Vaccine Alone and in Combination Treatment in HER2 Cancer Patients

NCT04246671

Description:

A Phase 1/2 open label trial of intravenous administration of TAEK-VAC-HerBy vaccine in patients with advanced HER2- expressing cancer. The study will be completed in 3 stages. In Stage 1 patients will be enrolled and treated according to a 3+3 dose escalation scheme. Up to 4 dose levels will be explored. Stage 2 will enroll patients with HER2- positive breast and gastric cancer to administer the TAEK-VAC-HerBy vaccine in combination with HER2 antibodies. Stage 3 will enroll patients to evaluate the safety and tolerability of the TAEK-VAC-HerBy vaccine in combination with HER2 antibodies and PD-1/PD-L1 antibody. Patients, in all three stages, will receive TAEK-VAC-HerBy every three weeks, three administrations in total.

Related Conditions:
  • Breast Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Intravenous TAEK-VAC-HerBy Vaccine Alone and in Combination Treatment in HER2 Cancer Patients
  • Official Title: Phase 1/2 Expansion Cohorts Trial of Intravenous Administration of TAEK-VAC-HerBy Vaccine Alone and in Combination With HER2- and PD-1/PD-L1 Antibodies in Patients With Advanced HER2-expressing Cancer

Clinical Trial IDs

  • ORG STUDY ID: TAEK-VAC-HerBy-001 Phase 1
  • NCT ID: NCT04246671

Conditions

  • Breast Cancer
  • Gastric Cancer
  • Cancer

Interventions

DrugSynonymsArms
TAEK-VAC-HerByTAEK-VAC-HerBy Stage 1 (TVH 1x10^10 Inf.U)

Purpose

A Phase 1/2 open label trial of intravenous administration of TAEK-VAC-HerBy vaccine in patients with advanced HER2- expressing cancer. The study will be completed in 3 stages. In Stage 1 patients will be enrolled and treated according to a 3+3 dose escalation scheme. Up to 4 dose levels will be explored. Stage 2 will enroll patients with HER2- positive breast and gastric cancer to administer the TAEK-VAC-HerBy vaccine in combination with HER2 antibodies. Stage 3 will enroll patients to evaluate the safety and tolerability of the TAEK-VAC-HerBy vaccine in combination with HER2 antibodies and PD-1/PD-L1 antibody. Patients, in all three stages, will receive TAEK-VAC-HerBy every three weeks, three administrations in total.

Trial Arms

NameTypeDescriptionInterventions
TAEK-VAC-HerBy Stage 1 (TVH 1x10^7 Inf.U)ExperimentalTAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^7 Inf.U.
  • TAEK-VAC-HerBy
TAEK-VAC-HerBy Stage 1 (TVH 1x10^8 Inf.U)ExperimentalTAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^8 Inf.U.
  • TAEK-VAC-HerBy
TAEK-VAC-HerBy Stage 1 (TVH 1x10^9 Inf.U)ExperimentalTAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^9 Inf.U.
  • TAEK-VAC-HerBy
TAEK-VAC-HerBy Stage 1 (TVH 1x10^10 Inf.U)ExperimentalTAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^10 Inf.U.
  • TAEK-VAC-HerBy
TAEK-VAC-HerBy Stage 2 - (Trastuzumab + TVH)ExperimentalTAEK-VAC-HerBy will be administered to patients who are on stable dose of Trastuzumab. TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total.
  • TAEK-VAC-HerBy
TAEK-VAC-HerBy Stage 2 - (T-DM1 + TVH)ExperimentalTAEK-VAC-HerBy will be administered to patients who are on stable dose of T-DM1. TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total.
  • TAEK-VAC-HerBy
TAEK-VAC-HerBy Stage 2 - (Trastuzumab + Pertuzumab + TVH)ExperimentalTAEK-VAC-HerBy will be administered intravenously to patients who are on stable dose of Trastuzumab and Pertuzumab. TAEK-VAC-HerBy will be administered every three weeks with three administrations in total.
  • TAEK-VAC-HerBy
TAEK-VAC-HerBy Stage 2 - (Her2 + TVH + PD1/PD-L1)ExperimentalTAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total in combination with a HER2 antibody and a PD-1/PD-L1 Antibody.
  • TAEK-VAC-HerBy

Eligibility Criteria

        Inclusion Criteria:

          1. Men and women > 18 years old.

          2. Patients must be able to understand and be willing to sign a written informed consent
             document.

          3. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other trial procedures.

          4. Patients must have a metastatic or recurrent locally advanced malignant tumor,
             histologically documented.

          5. Patients must have completed or had disease progression on at least one prior line of
             disease-appropriate therapy for locally advanced or metastatic disease, or not be
             candidates for therapy of proven efficacy for their disease.

          6. ECOG performance status 0 or 1

          7. Patients must have normal organ and bone marrow function as defined below:

               -  Renal function:

             Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥
             40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = [(140 - age in
             years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL] Male CrCl = [(140 -
             age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL] •Liver
             function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 x
             the ULN. Total bilirubin ≤ 1.5 x ULN (in subjects with Gilbert's syndrome a total
             bilirubin ≤ 3.0 x ULN), or < 5 x ULN, if liver metastases are present.

             •Hematological parameters (within one week of starting therapy):

             •Hemoglobin > 9 g/dL.

             •Platelet count ≥ 100,000/µL.

             •Absolute neutrophil count (ANC) ≥ 1/µL.

          8. Normal left ventricular ejection fraction (LVEF) ≥50%.

          9. Troponin I within normal limits.

         10. A maximum cumulative dose of prior doxorubicin ≤ 360 mg/m2 or epirubicin ≤ 720 mg/m2

         11. Any prior chemotherapy, targeted therapy, immunotherapy and/or radiation must be
             completed at least 4 weeks prior to the first planned dose of TVH vaccine, with the
             following exceptions, assuming any toxicity related to these therapies is well
             controlled or resolved and the patient has been on that therapy for at least 8 weeks
             at the time of enrollment:

               -  Breast cancer - patients may remain on hormonal therapy if indicated (Estrogen
                  Receptor/Progesterone Receptor positive [ER/PR+]).

         12. Patients must have recovered (Grade 1 or baseline) from any clinically significant
             toxicity associated with prior therapy.

         13. Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy
             test within 24 hours prior to administration of TVH vaccine or HER2-targeting
             antibodies. Both men and women must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) through the trial treatment period and
             for at least 3 months after the last vaccination therapy for TAEK-VAC-HerBy
             monotherapy (Stage 1) and 7 months for combination treatment arms (Stage 2 and 3).

             ADDITIONAL INCLUSION CRITERIA FOR STAGE 1 ONLY

         14. Patient population:

             •Patients with metastatic cancer with a high probability of brachyury expression (such
             as lung, breast, ovarian, prostate, colorectal, pancreatic, hepatocellular, Merkel
             cell, small cell lung cancer or chordoma; other tumors may be included as data on the
             level of brachyury in those tumors becomes available) and have progressed on at least
             two lines of systemic therapy.

             •Patients with unresectable locally advanced and metastatic breast and
             gastric/gastroesophageal junction cancer expressing HER2 at levels lower than the
             threshold required for definition of HER-2 positivity by ASCO/CAP.

               -  Other unresectable locally advanced or metastatic cancers (such as ovarian,
                  bladder, salivary gland, endometrial, pancreatic and non-small-cell lung cancer
                  NSCLC, etc) with HER2 amplification by adjusted fold change detected by NGS, FISH
                  detected HER2/CEP17 ≥2, or any level of HER2 detected by IHC are acceptable since
                  no HER2 targeted therapy is FDA-approved for those indications. Patients that are
                  enrolled with tumors having HER2 expression below the threshold required for
                  definition of HER2 positivity by ASCO/CAP must have progressed on at least two
                  lines of systemic therapy.

               -  Patients with breast and gastric HER2- positive tumors as per ASCO/CAP must have
                  progressed after receipt of all therapies known to confer clinical benefit:
                  oBreast: trastuzumab, pertuzumab, T-DM1. These patients may have also received
                  tyrosine kinase inhibitors (TKI) such as lapatinib or neratinib as well as
                  different lines of chemotherapy. oGastric and gastroesophageal junction cancer:
                  at the time of progression after trastuzumab in combination with chemotherapy as
                  first line therapy.

         15. Patients must have measurable or evaluable disease. Measurable disease is defined by
             RECIST 1.1. In the case of evaluable disease, patients should have cancer-related
             symptoms to justify risk. Evaluable disease is defined as any of the following:

               -  Elevated serum tumor marker known to be related to the patient's tumor burden.

               -  Clear radiographic or physical exam evidence of tumor which does not meet RECIST
                  1.1 measurability criteria.

        ADDITIONAL INCLUSION CRITERIA FOR STAGES 2 AND 3

        14. Patients must have measurable disease by computed tomography (CT)/ magnetic resonance
        imaging (MRI) per RECIST 1.1

        15. Patient population:

        •Cohort 2 will include patients with HER2-positive tumors (breast, gastric).

          -  Cohorts 3 and 4 will include only patients with metastatic HER2-positive breast
             cancer: oCohort 3 will include patients with less than CR to T-DM1 treatment (SD, PR)
             or patients at the first evidence of progression while on T-DM1 treatment and before
             initiating an alternative systemic treatment oCohort 4 will include patients on
             treatment with trastuzumab plus pertuzumab with less than CR (PR or SD) or as a window
             of opportunity at the first evidence of progression and before initiating the next
             line of standard treatment

          -  Cohort 5 will include patients with treatment combination used for a cohort of Stage 2
             which completed recruitment first (or a subgroup of 6 patients within the Cohort 2: 2a
             (breast) or 2b (gastric). The cohort needs to satisfy criteria listed above.

             16. HER2 status must be determined as defined by the most recent ASCO/CAP guidelines
             for breast and gastric/gastroesophageal cancer.

             17. For Cohort 2, 3 and 4, patients must be on a stable dose of HER2 antibody(ies).
             Patient is defined to be on a stable dose of HER2 antibody(ies) if they have completed
             the chemotherapy component of regimens consisting on the combination of chemotherapy
             with HER2-targeting antibodies and have continued with the antibody for a minimum of 2
             months.

        ADDITIONAL INCLUSION CRITERIA FOR STAGE 3

        18. Availability of formalin fixed paraffin embedded (FFPE) tumor sample (consecutive 10 x
        4µm sections, not older than 3 years) for PD-L1 expression determination. Result
        availability is not mandatory for patient inclusion into the trial.

        19. Patients must be immune check-point inhibitor treatment naïve.

        Exclusion Criteria:

          1. Receipt of an investigational agent within 28 days of the first planned dose of TVH
             vaccine.

          2. Concurrent chemotherapy or radiotherapy or other immunotherapy not explicitly allowed
             by inclusion criteria for that stage of the trial.

          3. During the Stage 2 and 3, patients with history of other malignancies within last 5
             years with an estimated risk of recurrence higher than 50% are excluded. Examples of
             low risk of recurrence malignancies are non-melanoma skin cancer, in situ cervical,
             superficial bladder cancer, etc.

          4. Known metastatic disease to the central nervous system, unless previously treated and
             responded with a minimum stable disease over 2 CT scans separated at least 4 weeks
             from each other, and more than 6 weeks since the last dose of dexamethasone.

          5. History of allergy or untoward reaction to prior vaccination with vaccinia virus,
             aminoglycoside antibiotics, ciprofloxacin, or egg products.

          6. Active infection within 72 hours prior to vaccination.

          7. Administration of antibiotics within 7 days prior to initial vaccination.

          8. Subjects should have no known evidence of being immunocompromised as listed below:

               -  Human immunodeficiency virus (HIV) positivity, chronic hepatitis infection,
                  including B and C

               -  Active, known or suspected autoimmune disease. Subjects with vitiligo, type I
                  diabetes mellitus, residual hypothyroidism due to autoimmune condition only
                  requiring hormone replacement, and psoriasis not requiring systemic treatment are
                  permitted

               -  Immunosuppressive therapy, post-organ transplant

          9. Chronic administration (defined as > 5 consecutive days of > 15 mg of prednisone (or
             equivalent) per day) of systemic corticosteroids within 14 days of the first planned
             dose of TAEK-VAC-HerBy vaccine. Use of inhaled steroids, nasal sprays, eye drops, and
             topical creams is allowed. Steroids premedication for CT scans is allowed.

         10. Vaccinations or planned vaccinations with a live vaccine within 30 days prior to the
             trial vaccination or with an inactivated vaccine within 14 days prior to the trial
             vaccination.

         11. Pregnant or breastfeeding women.

         12. Clinically significant cardiomyopathy, coronary disease, congestive heart failure
             (NYHA class III or IV) or reduced as per institutional standards LVEF, poorly
             controlled hypertension (systolic > 180 mm Hg or diastolic > 100 mm Hg) or
             cerebrovascular accident within 1 year.

         13. Known history of, or any evidence of active, non-infectious pneumonitis or primary
             pulmonary fibrosis.

         14. Any other condition, which in the opinion of the Investigator, would indicate the
             subject is a poor candidate for treatment with TVH vaccine or would interfere with the
             evaluation of the trial endpoints.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Patients with Dose Limiting Toxicity (DLT)
Time Frame:DLT evaluation period is 30 days after the last vaccine dose
Safety Issue:
Description:Frequency of patients with DLTs

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bavarian Nordic

Trial Keywords

  • HER2-expressing tumors, HER2 antibodies, PD-1 inhibitor

Last Updated

August 11, 2020