Clinical Trials /

Phase 1 / 2 Study of AGEN2034 in Advanced Tumors and Cervical Cancer

NCT03104699

Description:

This is a 2-part trial: a Phase 1, open-label, dose-escalation study in subjects with metastatic or locally advanced solid tumors, with a consecutive Phase 2 expansion to evaluate efficacy in subjects with recurrent, unresectable, or metastatic (advanced) cervical cancer that has progressed after a platinum-based treatment regimen.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 / 2 Study of AGEN2034 in Advanced Tumors and Cervical Cancer
  • Official Title: Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN2034 in Subjects With Metastatic or Locally Advanced Solid Tumors, With Expansion to Second-Line Cervical Cancer

Clinical Trial IDs

  • ORG STUDY ID: C-700-01
  • NCT ID: NCT03104699

Conditions

  • Advanced Cancer
  • Cervical Cancer

Interventions

DrugSynonymsArms
AGEN2034AGEN2034

Purpose

This is a Phase 1, open-label, 3 + 3 dose-escalation trial in subjects with metastatic or locally advanced solid tumors, with a consecutive Phase 2 expansion to evaluate efficacy in subjects with recurrent, unresectable, or metastatic (advanced) cervical cancer that has progressed after a platinum doublet.

Trial Arms

NameTypeDescriptionInterventions
AGEN2034Experimentalanti-PD-1 antibody
  • AGEN2034

Eligibility Criteria

        Inclusion Criteria:

          -  Safety Cohort (Dose Escalation)

               1. Signed written informed consent.

               2. Age ≥18 years.

               3. Histologically or cytologically proven metastatic or locally advanced solid
                  tumors for which no standard therapy exists or standard therapy has failed.
                  Availability of tumor archival material or fresh biopsies is optional for
                  subjects in dose escalation.

               4. ECOG performance status of 0 to 1 at trial entry and estimated life expectancy
                  of ≥3 months.

               5. Evidence of objective disease. A measurable lesion is not necessary.

               6. Adequate hematological function defined by white blood cell (WBC) count ≥3 ×
                  10^9/L; absolute neutrophil count (ANC) ≥1.5 × 10^9/L; lymphocyte count ≥0.5 ×
                  10^9/L; platelet count ≥100 × 10^9/L; and hemoglobin ≥9 g/dL (may have been
                  transfused).

               7. Adequate hepatic function, defined as total bilirubin ≤1.5 × upper limit of
                  normal (ULN); AST ≤2.5 × ULN; and ALT ≤2.5 × ULN. For subjects with documented
                  metastatic disease to the liver, AST and ALT: ≤5 × ULN.

               8. Adequate renal function, defined as estimated creatinine clearance >50 mL/min
                  according to Cockcroft-Gault formula or measured 24-hour creatinine clearance
                  (or local institutional standard method).

               9. Effective contraception for both male and female subjects if risk of conception
                  exists.

          -  Efficacy Expansion Cohort (Second-Line Cervical Cancer)

               1. Signed written informed consent.

               2. Age ≥18 years.

               3. Subjects must have recurrent, unresectable, or metastatic cervical cancer and
                  have relapsed after a platinum-containing doublet administered for treatment of
                  advanced (recurrent, unresectable, or metastatic) disease.

                  Subjects must have persistent, recurrent, or metastatic squamous cell carcinoma,
                  adenosquamous carcinoma or adenocarcinoma of the cervix, with documented disease
                  progression (disease not amenable to curative therapy).

                  Note: The following cervical tumors are not eligible: minimal deviation/adenoma
                  malignum, gastric type adenocarcinoma, clear cell carcinoma and mesonephric
                  carcinoma. Histologic confirmation of the original primary tumor is required via
                  pathology report.

                  Subjects must have had one prior systemic chemotherapeutic regimen for
                  management of persistent, recurrent, or metastatic carcinoma of the cervix
                  (e.g., paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab). Chemotherapy
                  administered concurrently with primary radiation (e.g., weekly cisplatin) is not
                  counted as a systemic chemotherapy regimen. Adjuvant chemotherapy given
                  following completion of radiation therapy (or concurrent chemotherapy and
                  radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.,
                  paclitaxel and carboplatin for ≤4 cycles).

                  Note: Subjects who have received >1 prior regimen are not eligible.

               4. ECOG performance status of 0 to 1 at trial entry and estimated life expectancy
                  of ≥3 months.

               5. Availability of a formalin-fixed paraffin-embedded block containing tumor tissue
                  or 7 unstained tumor slides suitable for PD-L1 expression assessment.

               6. Availability of tissue for HPV testing (paraffin block or one 7-µm section on a
                  slide).

               7. Disease must be measurable, with ≥1 unidimensional measurable lesion per RECIST
                  1.1.

               8. Adequate hematological function, defined as WBC ≥3 × 10^9/L; ANC ≥1.5 × 10^9/L;
                  lymphocyte count ≥0.5 × 10^9/L; platelet count ≥100 × 10^9/L; and hemoglobin ≥9
                  g/dL (may have been transfused).

               9. Adequate hepatic function, defined as total bilirubin ≤1.5 × ULN; AST ≤2.5 ×
                  ULN; and ALT ≤2.5 × ULN.

              10. Adequate renal function, defined as estimated creatinine clearance >30 mL/min
                  according to Cockcroft-Gault formula or measured 24-hour creatinine clearance
                  (or local institutional standard method).

              11. Effective contraception for both male and female subjects if risk of conception
                  exists. Note: Effects of the study drug on the developing human fetus are
                  unknown. Thus, women of childbearing potential and men must agree to use
                  effective contraception, defined as 2 barrier methods, or 1 barrier method with
                  a spermicide, an intrauterine device or use of oral female contraceptive.
                  Effective contraception must be used 30 days before first study drug
                  administration, for the duration of trial participation, and ≥60 days after
                  stopping trial participation. Should a woman become pregnant or suspect she is
                  pregnant while she or her partner is participating in this trial, the treating
                  physician should be informed immediately.

        Exclusion Criteria:

          -  Safety and Expansion Cohorts

               1. Concurrent treatment with a non-permitted drug.

               2. Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins
                  (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic
                  T-lymphocyte antigen 4 (CTLA-4) antibodies. For subjects with metastatic
                  melanoma, prior treatment with CTLA-4-blocking antibody is permissible.

               3. Concurrent anticancer treatment (e.g., cytoreductive therapy, radiotherapy
                  except for palliative bone-directed radiotherapy, immune therapy, or cytokine
                  therapy except for erythropoietin) within 28 days before start of trial
                  treatment; major surgery within 28 days before start of trial treatment
                  (excluding prior diagnostic biopsy); use of hormonal agents within 7 days before
                  start of trial treatment, except for subjects with castration-resistant prostate
                  cancer (CRPC), who may remain on treatment with luteinizing hormone-releasing
                  hormone agonists or antagonists; or use of any investigational drug within 28
                  days before start of trial treatment.

                  Note: Small molecule or antibody targeted therapy is permissible <14 days from
                  start of trial treatment.

               4. Subjects receiving immunosuppressive agents (such as steroids) for any reason
                  should be tapered off these drugs 14 days before initiation of study treatment.
                  Steroids with no or minimal systemic effect (topical, inhalation) are allowed.

                  Note: Subjects receiving bisphosphonate or denosumab are eligible provided that
                  treatment was initiated ≥14 days before first dose of AGEN2034.

                  Note: Use of inhaled or topical corticosteroid is permitted. Note: Steroid
                  pre-medication for radiographic imaging for dye allergies is permitted.

               5. Previous malignant disease (other than target malignancy to be investigated in
                  this trial) within the last 5 years, with the exception of basal or squamous
                  cell carcinoma of the skin.

               6. Rapidly progressive disease.

               7. Active or history of central nervous system metastases.

               8. Receipt of any organ transplantation, including allogeneic stem-cell
                  transplantation.

               9. Significant acute or chronic infections, including:

                    -  Known history of testing positive for human immunodeficiency virus (HIV) or
                       known acquired immunodeficiency syndrome (AIDS).

                    -  Positive test for hepatitis B virus (HBV) surface antigen and/or
                       confirmatory hepatitis C virus (HCV) RNA (if anti-HCV antibody tested
                       positive).

              10. Active or history of any autoimmune disease (subjects with diabetes type 1,
                  vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring
                  immunosuppressive treatment are eligible) or immunodeficiencies.

              11. Known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE
                  grade ≥3), any history of anaphylaxis, or uncontrolled asthma (i.e., ≥3 features
                  of partly controlled asthma).

              12. Persisting toxicity related to prior therapy of NCI CTCAE grade >1 severity.
                  Sensory neuropathy of grade ≤2 is acceptable.

              13. Pregnancy or breast feeding.

              14. Known alcohol or drug abuse.

              15. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
                  accident/stroke (<6 months before enrollment), myocardial infarction (<6 months
                  before enrollment), unstable angina, congestive heart failure (New York Heart
                  Association class ≥II), or serious uncontrolled cardiac arrhythmia requiring
                  medication.

              16. All other significant diseases (e.g., inflammatory bowel disease) that, in the
                  opinion of the investigator, might impair the subject's tolerance of trial
                  treatment.

              17. Any psychiatric condition that would prohibit understanding or rendering of
                  informed consent.

              18. Legal incapacity or limited legal capacity.

              19. Vaccination within 4 weeks of first dose of AGEN2034 and while on study except
                  for administration of inactivated vaccines (e.g., inactivated influenza
                  vaccines).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicities (DLTs) of AGEN2034
Time Frame:3 weeks
Safety Issue:
Description:Occurrence of DLTs during first 3 weeks of treatment in the dose escalation part of the study

Secondary Outcome Measures

Measure:Maximum Plasma Concentration (Cmax) of AGEN2034
Time Frame:1 year
Safety Issue:
Description:Understanding PK
Measure:Area Under the Curve (AUC) of AGEN2034
Time Frame:1 year
Safety Issue:
Description:Understanding PK
Measure:Progression-free survival (PFS)
Time Frame:1 year
Safety Issue:
Description:Time from first treatment to first observation of documented disease progression
Measure:Duration of response (DOR)
Time Frame:1 year
Safety Issue:
Description:Time from first observation of response to first observation of documented disease progression
Measure:Overall survival (OS)
Time Frame:1 year
Safety Issue:
Description:Time from first treatment to death

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Agenus Inc.

Trial Keywords

  • Antibodies
  • Immunologic effects
  • Physiological Effects of Drugs

Last Updated

April 17, 2017