A Study of PLX2853 in Advanced Malignancies.

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Brief Title

A Study of PLX2853 in Advanced Malignancies.

Official Title

A Phase 1b/2a Dose-escalation Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX2853 in Subjects With Advanced Malignancies

Brief Summary

      The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics
      and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced
      malignancies.
    


Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

Secondary Outcome

 Overall response rate (ORR) defined according to standard criteria for the relevant malignancy [Phase1b]

Condition

Small Cell Lung Cancer

Intervention

PLX2853

Study Arms / Comparison Groups

 PLX2853
Description:  Phase 1b (Dose Escalation): Approximately 45 subjects with advanced malignancies to establish the MTD/RP2D. Up to 6 additional subjects may be enrolled at the MTD/RP2D as a dose confirmation.
Phase 2a (Dose Expansion): There will be 5 total expansion cohorts. Either 10 or 29 subjects per cohort in each of 4 expansion cohorts: advanced SCLC, uveal melanoma, OCCC, and any other advanced malignancy with a known ARID1A mutation (between 40 to 116 subjects total for the solid tumor expansion phase). For the 5th expansion cohort, up to 20 subjects may be enrolled for NHL.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

166

Start Date

September 12, 2017

Completion Date

June 2022

Primary Completion Date

December 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of one of the following:

          -  Phase 1b:

               -  Histologically confirmed advanced refractory solid tumor that is measurable or
                  evaluable per RECIST 1.1 criteria.

               -  Histologically confirmed NHL: diffuse large B-cell lymphoma and follicular
                  lymphoma (Grade 1-3A) which is measurable or evaluable per Lugano criteria, has
                  progressed following at least 1 line of prior anticancer therapy.

          -  Phase 2a: Patients with various solid tumors or NHL who have received prior therapy.

          -  Age ≥18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

          -  Adequate organ function as appropriate for the disease under study. All screening
             laboratory tests should be performed within 10 days of treatment initiation.

          -  Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at
             Screening (≤7 days prior to 1st study drug dose) and must agree to use an effective
             form of contraception from the time of the negative pregnancy test up to 90 days after
             the last dose of study drug. Effective forms of contraception include abstinence,
             hormonal contraceptive in conjunction with a barrier method, or a double barrier
             method. Women of non-child-bearing potential may be included if they are either
             surgically sterile or have been postmenopausal for ≥1 year.

          -  Fertile men must agree to use an effective method of birth control during the study
             and for up to 90 days after the last dose of study drug.

          -  All associated clinically significant drug-related toxicity from previous cancer
             therapy must be resolved prior to study treatment administration (alopecia, erectile
             impotence, hot flashes, decreased libido, and neuropathy is allowed).

          -  Willingness and ability to provide written informed consent prior to any study-related
             procedures and to comply with all study requirements

        Exclusion Criteria:

          -  Prior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610

          -  Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade 2

          -  Autoimmune hemolytic anemia or autoimmune thrombocytopenia

          -  Presence of symptomatic or uncontrolled central nervous system or leptomeningeal
             metastases

          -  Known or suspected allergy to the investigational agent or any agent given in
             association with this trial

          -  Clinically significant cardiac disease such as cardiac arrhythmias including
             bradyarrhythmias and/or subjects who require anti-arrhythmic therapy (excluding beta
             blockers or digoxin), including uncontrolled hypertension or arterial or venous
             thrombotic events. Subjects with controlled atrial fibrillation are not excluded.

          -  Inability to take oral medication or significant nausea and vomiting, malabsorption,
             or significant small bowel resection that, in the opinion of the Investigator, would
             preclude adequate absorption

          -  Non-healing wound, ulcer, or bone fracture

          -  Subject has known human immunodeficiency virus (HIV), hepatitis B or hepatitis C
             infection or is known to be a carrier of hepatitis B or C. Subjects who are positive
             for hepatitis C virus (HCV) antibody must be negative for HCV by polymerase chain
             reaction (PCR) to be eligible. Subjects with occult or prior hepatitis B virus (HBV)
             infection (defined as positive total hepatitis B core antibody (HBcAb) and negative
             hepatitis B surface antigen (HBsAg) may be included if HBV DNA is undetectable. These
             subjects must be willing to undergo additional testing per local standard of care.

          -  Active second malignancy with the exception of any of the following:

               -  Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or
                  in situ cervical cancer;

               -  Adequately treated Stage I cancer from which the subject is currently in
                  remission and has been in remission for ≥2 years;

               -  Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10
                  ng/mL; or

               -  Any other cancer from which the patient has been disease-free for ≥3 years.

          -  Subjects with documented hepatic metastases involving >50% of the hepatic parenchyma,
             or any individual liver metastasis >5 cm, as assessed by the investigator.

          -  Major surgery or significant traumatic injury within 14 days prior to Cycle 1 Day 1

          -  Receipt of anti-cancer therapy with insufficient washout prior to Cycle 1 Day 1: No
             chemotherapy, radiation therapy, or small molecule tyrosine kinase inhibitors (TKI)
             for the treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of
             Cycle 1 Day 1. Certain standard of care hormonal anticancer therapies, such as agents
             targeted to GnRH for the treatment of prostate cancer or aromatase inhibitors for the
             treatment of breast cancer, may be permitted after consultation with the medical
             monitor. No immune therapy or other biologic therapy (other monoclonal antibodies or
             antibody-drug conjugates [ADCs]) for the treatment of cancer within 28 days of Cycle 1
             Day 1.

          -  Subject is receiving systemic steroids at doses greater than the equivalent of
             prednisone 10 mg daily, with the exception of intermittent use for the treatment of
             emesis

          -  Subject is participating in any other therapeutic clinical study (observational or
             registry trials are allowed)

          -  Female subjects who are pregnant or breast-feeding

          -  Presence of any other medical, psychological, familial, sociological, or geographic
             condition potentially hampering compliance with the study protocol or would interfere
             with the study endpoints or the subject's ability to participate in the study in the
             judgement of the investigator
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 510-647-4148, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03297424

Organization ID

PLX124-01


Responsible Party

Sponsor

Study Sponsor

Plexxikon


Study Sponsor

, , 


Verification Date

August 2021