Clinical Trials /

BDB001-102 Open Label Dose Escalation Combination w Atezolizumab

NCT04196530

Description:

A Phase 1 Open-label Dose Escalation Study of BDB001 in Combination with Atezolizumab in Subjects with Advanced Solid Tumors

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: BDB001-102 Open Label Dose Escalation Combination w Atezolizumab
  • Official Title: Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in Combination With Atezolizumab in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BDB001-102
  • NCT ID: NCT04196530

Conditions

  • Tumor, Solid

Interventions

DrugSynonymsArms
BDB001Dose Escalation of BDB001 with atezolizumab
AtezolizumabTecentriqDose Escalation of BDB001 with atezolizumab

Purpose

A Phase 1 Open-label Dose Escalation Study of BDB001 in Combination with Atezolizumab in Subjects with Advanced Solid Tumors

Detailed Description

      This clinical trial is a study of an experimental drug called BDB001. BDB001 is a Toll-like
      receptor (TLR) agonist that activates the immune system.

      The primary objectives of this study are to evaluate the safety and tolerability of BDB001 in
      combination with atezolizumab (Tecentriq) in subjects with unresectable or metastatic solid
      tumors who have relapsed or are refractory to standard treatment or for whom there is no
      approved therapy.

      This is a multi-center, open-label, dose escalation/dose expansion Phase 1 study of BDB001 in
      combination with atezolizumab.

      The study will be conducted in two separate but independent parts: a dose escalation part
      with BDB001 and atezolizumab and a dose expansion part of BDB001 in combination with
      atezolizumab.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation of BDB001 with atezolizumabExperimentalThis part of the study will follow a traditional 3+3 dose escalation design. Each successive group of patients will be enrolled at an incrementally higher dosage until the Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D) of BDB001 with atezolizumab is reached.
  • BDB001
  • Atezolizumab
Dose Expansion of BDB001 with atezolizumabExperimentalAt the end of the dose escalation part of the study, the BDB001 dose to be used in combination with atezolizumab in the expansion part of the study will be established after thorough review of all available safety, preliminary efficacy, PK and PD data. A biologically active dose will be selected that is either the MTD, if one was established in the escalation part, or an RP2D if no MTD was established. Approximately 20 additional subjects will initially be enrolled in the dose expansion part.
  • BDB001
  • Atezolizumab

Eligibility Criteria

        Inclusion

        Participants are eligible to be included in the study only if all of the following criteria
        apply:

          1. Be 18 years of age on day of signing informed consent

          2. Subjects with histologically or cytologically confirmed advanced or metastatic solid
             tumors who have disease progression after treatment with all available therapies for
             metastatic disease that are known to confer clinical benefit, or are intolerant to
             treatment, or refuse standard treatment. Note: there is no limit to the number of
             prior treatment regimens

          3. A male participant must agree to use contraception during the treatment period and for
             at least 120 days after the last dose of study treatment and refrain from donating
             sperm during this period

          4. A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and at least one of the following conditions applies:

               1. Not a woman of childbearing potential (WOCBP)

               2. A WOCBP who agrees to follow contraceptive guidance during the treatment period
                  and for at least 120 days after the last dose of study treatment

               3. A highly effective method of contraception is defined as one that results in a
                  low failure rate (i.e., less than 1% per year, when used consistently and
                  correctly)

          5. Evidence of progressive disease (PD) within 3 months of signing the informed consent
             form

          6. Have measurable disease with at least 1 lesion meeting measurable criteria per
             irRECIST as assessed by the local site investigator/radiology. Lesions situated in a
             previously irradiated area are considered measurable if progression has been
             demonstrated in such lesions

          7. Eastern Cooperative Oncology Group (ECOG) score of 0 - 2

          8. Minimum life expectancy of 3 months

          9. Have adequate organ function. Specimens must be collected within 10 days prior to the
             start of study treatment.

               -  Hematological: ANC ≥1500/µL; Platelets ≥100 000/µL; Hemoglobin ≥9.0 g/dL or ≥5.6
                  mmol/L

               -  Renal: serum creatinine ≤ 1.5 times the ULN or estimated creatinine clearance ≥
                  60 mL/min (Cockcroft and Gault formula
                  [http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/])

               -  Hepatic: Total bilirubin ≤1.5 ×ULN or direct bilirubin ≤ULN for participants with
                  total bilirubin levels >1.5 × ULN; AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN
                  for participants with liver metastases)

               -  Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 x ULN

         10. Recovery (to baseline or to Grade 1 or less) from prior treatment-related toxicities
             except alopecia. Participants with ≤Grade 2 neuropathy may be eligible. Note: If
             participant received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting study treatment.

         11. Ability to comply with treatment, laboratory monitoring and required clinic visits

         12. The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial

        Exclusion

        Participants are excluded from the study if any of the following criteria apply:

          1. A Woman of Child Bearing Potential 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

          2. Prior exposure to TLR 7 agonists, such as GS-9620, imiquimod, TMX 101, resiquimod,
             MEDI9197, and 825A, or TLR 9 agonists such as SD-101, tilsotolimod (IMO-2125),
             MGN1703, GNKG168, DUK-CPG-001 and CMP-001 for treatment of the solid tumor the subject
             is currently being evaluated for treatment with BDB001.

          3. 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 such as
             CTLA-4, OX40, and CD137, and was discontinued from that treatment due to a Grade 3 or
             higher irAE.

          4. Received previous therapy for malignancy within 21 days prior to administration of
             study drug, including any investigational agents (other than BDB001), chemotherapy,
             immunotherapy, biological or hormonal therapy. Subjects receiving systemic interferons
             or IL-2 must have discontinued the drug 4 weeks or 5 half-lives (whichever is longer)
             prior to initiation of study treatment because these drugs could potentially increase
             the risk of autoimmune conditions when given in combination with atezolizumab.
             Subjects receiving nitrosoureas or mitomycin C must have discontinued the drug 6 weeks
             prior to initiation of study treatment.

          5. Subjects who are receiving a RANKL inhibitor such as denosumab prior to enrollment
             must be willing and eligible to receive a bisphosphonate instead; denosumab could
             potentially alter the activity and the safety of atezolizumab.

          6. Major surgery within 4 weeks of first dose of study drug

          7. Has received prior radiotherapy within 2 weeks of start of study treatment.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease

          8. 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

          9. Currently receiving medications known to be strong inhibitors of CYP1A and CYP3A and
             strong/moderate inducers of CYP1A and CYP3A

         10. Receiving systemic steroid therapy or any other form of immunosuppressive therapy
             within 7 days prior to the first dose of study drug. The use of physiologic doses of
             corticosteroids may be approved after consultation with the Sponsor.

         11. Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 21 days prior to the first dose of
             study treatment. Note: Participants who have entered the follow-up phase of an
             investigational study may participate as long as it has been 21 days after the last
             dose of the previous investigational agent

         12. History within last 6 months of New York Heart Association Class III or IV heart
             failure, acute myocardial infarction, angina pectoris, uncontrolled arrhythmia, acute
             coronary syndromes, stent placement, uncontrolled hypertension

         13. QTc interval value > 470 msec (using Fridericia's Correction)

         14. Left ventricular ejection fraction (LVEF) < 50% by echocardiogram (ECHO) or multigated
             acquisition (MUGA) scan

         15. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
             previously treated brain metastases may participate provided they are radiologically
             stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
             (note that the repeat imaging should be performed during study screening), clinically
             stable and without requirement of steroid treatment for at least 14 days prior to
             first dose of study treatment (Kim 2017). Brain MRI is preferred to document stability
             of existing brain metastases. If MRI is medically contraindicated, CT with contrast is
             an acceptable alternative.

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

         17. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is
             required unless mandated by local health authority

         18. Known active hepatitis A, B or C. Subjects who are HBsAg+ and have DNA load < 2000
             IU/mL (104 copies/mL) are eligible to participate in the study provided they meet the
             ALT and bilirubin inclusion criteria.

         19. Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years with the exception of basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin that has undergone potentially curative therapy,
             in situ cervical cancer, prostate cancer that is not actively being treated, and
             malignancies which have been treated with curative surgery and have not recurred.

         20. Has an active infection requiring systemic therapy

         21. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the participant's
             participation for the full duration of the study, or is not in the best interest of
             the participant to participate, in the opinion of the treating investigator

         22. Has a known psychiatric or substance abuse disorder that would interfere with the
             participant's ability to cooperate with the requirements of the study

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

         24. Has had an allogenic tissue/solid organ transplant

         25. Active autoimmune disease that has required systemic treatment in past 2 years (i.e.,
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
             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 and is allowed.

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

         27. History of interstitial lung disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Tolerability: incidence of adverse events and any dose limiting toxicity
Time Frame:up to 21 months
Safety Issue:
Description:Safety and tolerability of BDB001 in combination with atezolizumab as measured by the incidence of adverse events and any dose limiting toxicities (DLT)

Secondary Outcome Measures

Measure:Radiographic Determination of Tumor Response after BDB001 in combination with atezolizumab dosing
Time Frame:At the beginning of Cycle 3 (every cycle is 21 days) up to 30 months after the first dose for each patient
Safety Issue:
Description:Radiographic determination of tumor response in subjects dosed with BDB001 and atezolizumab using irRECIST

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Birdie Biopharmaceuticals HK Limited

Trial Keywords

  • TLR
  • Immuno-oncology

Last Updated

December 11, 2019