Clinical Trials /

BDB001-101: Clinical Study of BDB001 as a Mono-therapy or in Combination With Pembrolizumab



Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in combination with Pembrolizumab in Subjects with Advanced Solid Tumors

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: BDB001-101: Clinical Study of BDB001 as a Mono-therapy or in Combination With Pembrolizumab
  • Official Title: Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BDB001-101
  • NCT ID: NCT03486301


  • Tumor, Solid


BDB001BDB001 in Combination with Pembrolizumab
PembrolizumabBDB001 in Combination with Pembrolizumab


Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in combination with Pembrolizumab 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 as
      a single agent and in combination with pembrolizumab and to determine the maximum tolerated
      dose (MTD) or the recommended Phase 2 dose (RP2D) when given in combination with
      pembrolizumab in subjects with advanced solid tumors.

      This is a multi-center, open-label, dose escalation/dose expansion Phase 1 study of BDB001 as
      a single agent and in combination with pembrolizumab in subjects with
      histologically-confirmed, incurable, unresectable or metastatic solid tumors that have
      relapsed or are refractory to standard therapies or for whom there is no approved therapy.

      The study will be conducted in two separate but independent dose escalation arms: a single
      agent arm (BDB001 alone) and a combination arm (BDB001 in combination with pembrolizumab).

      Participants will be allowed to continue treatment beyond study termination until occurrence
      of significant treatment-related toxicity, progressive disease or discontinuation criteria
      are met.

Trial Arms

Single Agent BDB001ExperimentalA single subject will be enrolled at each dose level in the single agent arm until any ≥ Grade 2 treatment-emergent adverse event (TEAE) is observed in the first cycle. Then dosage escalation 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 single agent BDB001 is reached.
  • BDB001
BDB001 in Combination with PembrolizumabExperimentalIn the combination arm of the study, a standard 3+3 dose escalation design will be utilized for all dose levels. When the MTD or RP2D of single agent BDB001 is reached, the first dose level cohort of the combination arm will begin. Once the MTD or RP2D in combination has been determined, twenty additional subjects will be enrolled in the expansion phase of the study.
  • BDB001
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria

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

          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 • 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

          6. Have measurable disease 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 as defined by the protocol. Specimens must be collected
             within 10 days prior to the start of study treatment.

        Exclusion Criteria

        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 (e.g., GS-9620, imiquimod, TMX 101, resiquimod,
             MEDI9197, 825A) and TLR 9 agonists (e.g., SD-101, IMO2125, MGN1703, GNKG168,
             DUK-CPG-001 and CMP-001) for treatment of the solid tumor the patient 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 (e.g.,
             CTLA-4, OX 40, 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 (6 weeks for nitrosoureas or mitomycin

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

          6. 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

          7. 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

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

          9. 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.

         10. 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 4 weeks after the last
             dose of the previous investigational agent

         11. 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

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

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

         14. 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).

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

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

         17. 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.

         18. 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 or
             in situ cervical cancer.

         19. Has an active infection requiring systemic therapy

         20. 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

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

         22. 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.

         23. Has had an allogenic tissue/solid organ transplant

         24. 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.

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

         26. 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 30 months
Safety Issue:
Description:Safety and tolerability of BDB001 as a single agent and in combination with pembrolizumab as measured by the incidence of adverse events and any dose limiting toxicity

Secondary Outcome Measures

Measure:Determine Maximum Tolerated Dose
Time Frame:From first dose to 21 days after first dose for each patient (cycle 1)
Safety Issue:
Description:Determination of the maximum tolerated dose by assessing the frequency of BDB001-related and BDB001 and pembrolizumab-related adverse events using CTCAE version 4.03 to categorize adverse event severity
Measure:Radiographic Determination of Tumor Response after BDB001 Dosing
Time Frame:Every 63 days (3 cycles) up to 30 months after the first dose for each patient (each cycle is 21 days)
Safety Issue:
Description:Radiographic determination of tumor response in subjects dosed with BDB001 and BDB001 and pembrolizumab using irRECIST


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

Trial Keywords

  • TLR
  • Immuno-oncology

Last Updated

July 14, 2021