Clinical Trials /

A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab

NCT03409458

Description:

This is a Phase 1b/2a, open-label, multi-center, non-randomized, dose-escalation study of PT-112 in combination with the anti-PD-L1 antibody, avelumab, in selected advanced solid tumors. The study is to be conducted in two parts: the Dose Escalation Phase of PT-112 within the combination and the Dose Confirmation Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose (RP2D) of PT-112 in the combination as avelumab will be administered at a flat dose of 800 mg. The trial will evaluate the PK (pharmacokinetic) effects of PT-112 and the safety and tolerability of the combination as well as preliminary clinical effects. The Dose Confirmation Phase will consist of two additional cohorts in patients with non-small cell lung cancer or urothelial carcinoma who will be treated at or below the MTD of PT-112 in the combination.

Related Conditions:
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab
  • Official Title: A Phase 1b/2a Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab

Clinical Trial IDs

  • ORG STUDY ID: PT-112-103-PAVE-1
  • NCT ID: NCT03409458

Conditions

  • Non Small Cell Lung Cancer (NSCLC)
  • Urothelial Carcinoma (UC)
  • Squamous Cell Carcinoma of the Head and Neck (SCCHN)
  • Metastatic Breast Cancer (mBC)
  • Castration-resistant Prostate Cancer (CRPC)

Interventions

DrugSynonymsArms
PT-112PT-112 in combination with avelumab
avelumabPT-112 in combination with avelumab

Purpose

This is a Phase 1b/2a, open-label, multi-center, non-randomized, dose-escalation study of PT-112 in combination with the anti-PD-L1 antibody, avelumab, in selected advanced solid tumors. The study is to be conducted in two parts: the Dose Escalation Phase of PT-112 within the combination and the Dose Confirmation Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose (RP2D) of PT-112 in the combination as avelumab will be administered at a flat dose of 800 mg. The trial will evaluate the PK (pharmacokinetic) effects of PT-112 and the safety and tolerability of the combination as well as preliminary clinical effects. The Dose Confirmation Phase will consist of two additional cohorts in patients with non-small cell lung cancer or urothelial carcinoma who will be treated at or below the MTD of PT-112 in the combination.

Detailed Description

      This is a Phase 1b/2a, open-label, multi-center, non-randomized, dose-escalation study of
      PT-112 in combination with the anti-PD-L1 antibody, avelumab, in selected advanced solid
      tumors. The study is to be conducted in two parts: the Dose Escalation Phase of PT-112 within
      the combination and the Dose Confirmation Phase. The Dose Escalation Phase will determine the
      Maximum Tolerated Dose (MTD) and recommended Phase 2 dose (RP2D) of PT-112 in the combination
      as avelumab will be administered at a flat dose of 800 mg. The trial will evaluate the PK
      (pharmacokinetic) effects of PT-112 and the safety and tolerability of the combination as
      well as preliminary clinical effects. The Dose Confirmation Phase will consist of two
      additional cohorts in patients with non-small cell lung cancer or urothelial carcinoma who
      will be treated at or below the MTD of PT-112 in the combination.
    

Trial Arms

NameTypeDescriptionInterventions
PT-112 in combination with avelumabExperimentalPT-112, administered by intravenous infusion avelumab, administered by intravenous infusion Patients with all listed conditions are eligible for treatment during the dose escalation phase of the study. Patients with NSCLC and mUC are eligible for the dose confirmation phase of the study.
  • PT-112
  • avelumab

Eligibility Criteria

        Key Inclusion Criteria:

          1. Histologically or cytologically proven metastatic or locally advanced disease.
             Specifically:

               -  patients with NSCLC, UC, mBC, or SCCHN must have measurable disease by RECIST
                  v1.1 criteria with at least one uni-dimensional measurable lesion;

               -  patients with CRPC must meet PCWG3 criteria for disease progression at trial
                  entry

          2. Availability of tumor specimens is mandatory for patients in the confirmation phase;

        2 ECOG Performance Status (PS) 0-1; 4 Estimated Life Expectancy > 3 months; 5 Adequate bone
        marrow (BM), renal, hepatic and metabolic function;

        Key Exclusion Criteria:

          1. Concurrent cancer treatment with cytoreductive therapy, radiotherapy, cytokine
             therapy, cytotoxic agents, targeted small molecule therapy or any investigational
             anticancer small molecule drugs within 2 weeks prior to the start of study treatment
             (except 5 weeks from last dose of nitrosourea compound) OR treatment with monoclonal
             antibodies within 4 weeks prior to the start of study treatment, with the following
             exceptions:

               -  PD-1 / PD-L1 checkpoint inhibitor therapy is permitted;

               -  Palliative bone-directed radiotherapy is permitted unless involving an area of ≥
                  25% of bone marrow reserves and occurring within 5 weeks prior to the start of
                  study treatment;

               -  Erythropoietin and darbopoietin-α are permitted;

               -  Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis (i.e., LHRH
                  agonist/antagonist) are permitted. No other hormonal therapy is permitted;

          2. Known symptomatic central nervous system (CNS) metastases requiring steroids. Patients
             with previously diagnosed CNS metastases are eligible if they (1) have completed their
             treatment and have recovered from the acute effects of radiation therapy and/or
             surgery prior to enrollment, (2) have discontinued corticosteroid treatment for these
             metastases for at least 14 days, and (3) are neurologically stable;

          3. Diagnosis of any other malignancy within 2 years prior to enrollment. However,
             adequately treated basal cell or squamous cell skin cancer or non-invasive superficial
             bladder cancer or carcinoma in situ of the bladder, breast or cervix; or prostate
             cancer of low grade (Gleason ≤6) or surveillance without any plans for treatment
             intervention (e.g., surgery, radiation, or castration) are allowed;

          4. Vaccination within 4 weeks of the first dose of study treatment is prohibited except
             for administration of inactivated vaccines;

          5. Current use of immunosuppressive medication at study entry, with the following
             exceptions:

               -  Intranasal, inhaled, or topical steroids or local steroid injections (eg,
                  intra-articular injection) are permitted;

               -  Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or
                  equivalent are permitted;

               -  Steroids as premedication for hypersensitivity reactions are permitted;

          6. Active or prior autoimmune disease that might deteriorate with receiving an
             immunostimulatory agent. However, patients with diabetes type 1, vitiligo, psoriasis,
             or hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are
             eligible;

          7. Acute or chronic infections requiring systemic therapy, including, among others:

               -  Active infection requiring systemic therapy;

               -  History of testing positive to human immunodeficiency virus (HIV) or known
                  acquired immunodeficiency syndrome;

               -  Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
                  (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is
                  positive);

               -  Active tuberculosis (history of exposure or history of positive TB test with
                  presence of clinical symptoms, physical or radiographic finding);

          8. Known history of autoimmune colitis, inflammatory bowel disease, pneumonitis,
             pulmonary fibrosis;

          9. Known intolerance to checkpoint inhibitor therapy, defined by the occurrence of an AE
             leading to drug discontinuation;

         10. Participation in other studies involving investigational drug(s) within 28 days prior
             to study entry and/or during study participation;
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended dose (RD) of PT-112 to be used in combination with avelumab for further studies in patients with advanced solid tumors.
Time Frame:24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Peak Plasma concentration (Cmax) for PT-112 Injection
Time Frame:24 months
Safety Issue:
Description:
Measure:Area under the plasma concentration versus time curve (AUC) for PT-112 Injection
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose-limiting toxicities (DLTs)
Time Frame:24 months
Safety Issue:
Description:
Measure:Number of patients with Adverse Events (AEs)
Time Frame:24 months
Safety Issue:
Description:
Measure:Tumor burden Assessment
Time Frame:24 months
Safety Issue:
Description:To be assessed by irRECIST criteria for NSCLC, SCCHN, mBC, and UC patients and by Prostate Cancer Working Group 3 (PCWG3) criteria for patients with CRPC
Measure:Overall Response Rate (ORR)
Time Frame:24 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:24 months
Safety Issue:
Description:
Measure:Median Progression-free Survival (mPFS)
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Phosplatin Therapeutics

Trial Keywords

  • Advanced Solid Tumors
  • NSCLC
  • mUC
  • mBC
  • CRPC
  • SCCHN

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