Clinical Trials /

AB-16B5 Combined With Docetaxel in Subjects With Metastatic Non-Small Cell Lung Cancer

NCT04364620

Description:

This Phase II study will recruit 40 metastatic non-small cell lung cancer patients who failed treatment with a platinum-containing doublet treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or sequentially. All recruited patients will receive AB-16B5 at a dose of 12 mg/kg once weekly combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AB-16B5 Combined With Docetaxel in Subjects With Metastatic Non-Small Cell Lung Cancer
  • Official Title: A Phase II Study of AB-16B5 Combined With Docetaxel in Previously Treated Subjects With Metastatic Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: AB-16B5-201
  • NCT ID: NCT04364620

Conditions

  • NSCLC Stage IV

Interventions

DrugSynonymsArms
AB-16B5Arm AB-16B5 and Docetaxel
DocetaxelArm AB-16B5 and Docetaxel

Purpose

This Phase II study will recruit 40 metastatic non-small cell lung cancer patients who failed treatment with a platinum-containing doublet treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or sequentially. All recruited patients will receive AB-16B5 at a dose of 12 mg/kg once weekly combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks.

Detailed Description

      This is an open-label, single-arm, multi-center Phase II trial of AB-16B5 in combination with
      docetaxel in previously treated subjects with metastatic non-small cell lung cancer who have
      experienced disease progression following treatment with a platinum-containing doublet
      treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or
      sequentially. Approximately 40 subjects will be enrolled in this trial and receive AB-16B5 at
      a dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75
      mg/m2 once every 3 weeks on Day 1. One cycle of treatment will consist of 21 days (3 weeks).
      The safety profile of the AB-16B5 and docetaxel combination will be examined during a safety
      lead-in period with the first 8 subjects completing one cycle of treatment. No dose
      escalation will be performed but a decision to de-escalate the AB-16B5 dose could be made
      using the modified toxicity probability interval method.

      Subjects will be evaluated every 6 weeks with radiographic imaging to assess response to
      treatment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for
      determination of the objective response rate (ORR) and progression free survival (PFS).
      Paired tumor biopsies (pre-treatment and on-treatment) will be collected in all subjects.
      Study treatment will continue until there is evidence of disease progression,
      treatment-related adverse events of unacceptable severity, subject request for
      discontinuation or Investigator determination that further treatment is not in the subject's
      best interest. Treatment through progression will be allowed if the Investigator considers
      the subject to be clinically stable. Subjects who must discontinue docetaxel due to toxicity
      will continue on AB-16B5.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AB-16B5 and DocetaxelExperimentalAB-16B5 at a dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks on Day 1.
  • AB-16B5
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects (male or non-pregnant female) must be ≥ 18 years of age on the day of signing
             the informed consent.

          -  Subjects with a histologically or cytologically confirmed diagnosis of (Stage III-IV)
             non-small cell lung cancer (NSCLC) and with at least one measurable lesion defined by
             RECIST 1.1.

          -  Subjects must have experienced a disease progression following treatment with a an
             anti-PD1 or PD-L1 immune checkpoint antibody and a platinum-containing doublet
             treatment, administered simultaneously or sequentially.

          -  Subjects with a targetable driver mutation in EGFR or ALK gene will be allowed on
             trial after failing all available targeted therapies and having experienced a disease
             progression following treatment with an anti-PD1 or PD-L1 immune checkpoint antibody
             and a platinum-containing doublet treatment, administered simultaneously or
             sequentially.

          -  Subjects must have adequate organ and immune function

          -  Subjects must have a tumor lesion amenable for biopsies with no contraindication for
             biopsy.

          -  Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             ≤ 2.

          -  Subjects must have a life expectancy of at least 3 months.

          -  Subjects must have recovered from the toxic effects resulting from the most recent
             cancer treatment to Grade 1 or less. If the subjects underwent major surgery or
             received radiation therapy, they must have recovered from the complications and/or
             toxicity.

          -  Female subjects of childbearing potential must have a negative urine or serum
             pregnancy test within 72 hours prior to the first dose of study treatment. If the
             urine test is positive or cannot be confirmed as negative, a serum pregnancy test will
             be required. The serum pregnancy test must be negative for the subject to be eligible.

          -  Subjects (both male and female) of reproductive potential must be willing to practice
             highly effective methods of contraception throughout the study and for up to 90 days
             after the last dose of study medication. Abstinence is acceptable if this is the
             subject's usual lifestyle.

          -  Female subjects are not considered of childbearing potential if they have a history of
             surgical sterility or evidence of post-menopausal status defined as any of the
             following:

               -  ≥ 45 years of age and has not had menses for more than 2 years.

               -  Amenorrhoeic for less than 2 years without hysterectomy and oophorectomy and a
                  follicle stimulating hormone (FSH) value in the postmenopausal range at
                  screening.

               -  Post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy or
                  oophorectomy must be confirmed with medical records of the actual procedure or by
                  ultrasound. Tubal ligation must be confirmed with medical records of the actual
                  procedure.

          -  Subjects must understand and be able and willing and likely to fully comply with the
             study procedures, including scheduled follow-up, and restrictions.

          -  Subjects must have given written personally signed and dated informed consent to
             participate in the study in accordance with the International Conference on
             Harmonization (ICH) Good Clinical Practice (GCP) Guidelines, before completing any
             study related procedures.

        Exclusion Criteria:

          -  Subjects who have received prior therapy with AB-16B5.

          -  Subjects who have received prior therapy with docetaxel for the treatment of NSCLC.

          -  Subjects who are currently participating or has participated in a study of an
             investigational agent or using an investigational device within 21 days prior to the
             first dose of study treatment. The 21-day window should be calculated using the last
             dose of an antineoplastic investigational agent or last use of an investigational
             device with antineoplastic intent.

          -  Subjects who have received any anti-cancer treatment within 3 weeks or radiation
             therapy within 2 weeks prior to receiving the first dose of study treatment or who
             have not recovered from adverse events to Grade 1 or less. Subjects with alopecia are
             eligible to participate.

          -  Subjects who are expected to require any other form of systemic or localized
             antineoplastic therapy while on the trial. This includes maintenance therapy with
             another agent or radiation therapy.

          -  Subjects who are receiving a dose > 10 mg/day of prednisone (or equivalent) within 7
             days prior to the first dose of study treatment or any other form of immunosuppressive
             medication (corticosteroid pre-treatment and/or post-treatment of docetaxel is
             allowed).

          -  Subjects who require treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole,
             itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir,
             ritonavir, saquinavir, telithromycin and voriconazole). Subjects may be included if
             there is an alternate treatment with a weak CYP3A4 inhibitor and they are willing to
             change prior to randomization. If the subject agrees to change from a strong inhibitor
             to a weak CYP3A4 inhibitor, the strong inhibitor must be stopped at least 7 days prior
             to the first dose of study treatment.

          -  Subjects who have another malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin or in situ cervical cancer.

          -  Subjects who have known active central nervous system metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate if they
             have been clinically stable for at least 2 weeks prior to the first dose of study
             treatment, if they have no evidence of new or enlarging brain metastases and if they
             are not receiving a dose > 10 mg/day of prednisone (or equivalent) within 7 days prior
             to the first dose of study treatment.

          -  Subjects with clinically significant ECG abnormalities.

          -  Subjects who have received or will receive a live vaccine within 30 days prior to the
             first dose of study treatment.

          -  Subjects with a known history of human immunodeficiency (HIV).

          -  Subjects with an active Hepatitis B or C infection.

          -  Subjects with an active infection requiring antibiotic therapy.

          -  Subjects with a known history of alcohol or other substance abuse within the last
             year.

          -  Subjects with known hypersensitivity to docetaxel.

          -  Subjects who have a history or current evidence of any condition, therapy or
             laboratory abnormalities that may confound the results of the trial, interfere with
             the subject's participation for the full duration of the trial or if it is not in the
             best interest of the subject to participate in the trial.

          -  Subjects with medical, social or psychosocial factors that, in the opinion of the
             treating Investigator, could impact the safety or compliance with study procedures.

          -  Subjects who are pregnant or lactating or who are expecting to conceive or father
             children within the projected duration of the trial through 90 days after the last
             dose of AB-16B5 or the last dose of docetaxel.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:2 years
Safety Issue:
Description:The percentage of subjects with radiologically complete or partial response as determined by the investigator according to RECIST version 1.1.

Secondary Outcome Measures

Measure:Clinical benefit rate (CBR)
Time Frame:2 years
Safety Issue:
Description:The percentage of subjects with complete response (CR), partial response (PR) and stable disease (SD) as determined by the investigator according to RECIST version 1.1.
Measure:Duration of response (complete response and partial response)
Time Frame:2 years
Safety Issue:
Description:The duration of complete and partial response as determined by the investigator according to RECIST version 1.1.
Measure:Duration of stable disease
Time Frame:2 years
Safety Issue:
Description:The duration of stable disease as determined by the investigator according to RECIST version 1.1.
Measure:Progression free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:Progression free survival measured from the date of study enrolment to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first).
Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:Overall survival measured from date of study enrolment to death from any cause.
Measure:Determination of plasma concentrations of AB-16B5
Time Frame:2 years
Safety Issue:
Description:Noncompartmental analysis of pharmacokinetic data using standard approaches. The pharmacokinetic data may also be evaluated using a population pharmacokinetics approach.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Alethia Biotherapeutics

Trial Keywords

  • Lung cancer
  • Chemotherapy

Last Updated

April 24, 2020