Clinical Trials /

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors

NCT04657068

Description:

This clinical trial is evaluating a drug called ART0380 in participants with advanced or metastatic solid tumors. The main goals of this study are to: - Find the recommended dose of ART0380 that can be given safely to participants alone and in combination with gemcitabine - Learn more about the side effects of ART0380 alone and in combination with gemcitabine - Learn more about the effectiveness of ART0380 alone and in combination with gemcitabine

Related Conditions:
  • Fallopian Tube Serous Adenocarcinoma
  • Malignant Solid Tumor
  • Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors
  • Official Title: A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy and in Combination to Patients With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ART0380C001
  • NCT ID: NCT04657068

Conditions

  • Advanced Cancer
  • Metastatic Cancer
  • Ovarian Cancer

Interventions

DrugSynonymsArms
ART0380Part A1
GemcitabineGemzarPart A2

Purpose

This clinical trial is evaluating a drug called ART0380 in participants with advanced or metastatic solid tumors. The main goals of this study are to: - Find the recommended dose of ART0380 that can be given safely to participants alone and in combination with gemcitabine - Learn more about the side effects of ART0380 alone and in combination with gemcitabine - Learn more about the effectiveness of ART0380 alone and in combination with gemcitabine

Detailed Description

      ART0380 is a new investigational medicinal product that is a potent and selective inhibitor
      of Ataxia telangiectasia and Rad3-related (ATR). ART0380 is being developed as an oral
      anti-cancer agent for the treatment of participants with cancers that harbor defects in
      deoxyribonucleic acid (DNA) repair and in combination with agents including those that cause
      DNA damage.

      This study is an open-label Phase I/IIa study designed to evaluate the safety, tolerability,
      PK and preliminary efficacy of ART0380 as monotherapy or in combination with gemcitabine in
      participants with advanced or metastatic solid tumors, advanced or solid tumors that fail to
      express Ataxia-Telangiectasia Mutated protein kinase (ATM) by immunohistochemistry, and high
      grade serous ovarian, primary peritoneal or fallopian tube carcinoma.
    

Trial Arms

NameTypeDescriptionInterventions
Part A1ExperimentalPart A1 will evaluate intermittent and continuous dosing of ART0380 monotherapy. Treatment will be given in 21 day cycles. Up to 68 participants will participate in this dose escalation arm.
  • ART0380
Part A2ExperimentalPart A2 will evaluate intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles. Up to 12 participants will participate in this dose escalation arm.
  • ART0380
  • Gemcitabine
Part B1ExperimentalPart B1 will evaluate ART0380 monotherapy in up to 40 participants with solid cancers that fail to express ATM (ataxia-telangiectasia mutated) protein.
  • ART0380
Part B2ExperimentalIn Part B2, up to 60 participants with platinum-resistant metastatic ovarian cancer will be randomized (open-label) 1:1 to either ART0380 in combination with gemcitabine or gemcitabine alone.
  • ART0380
  • Gemcitabine

Eligibility Criteria

        General Inclusion Criteria:

          -  Signed written informed consent

          -  Have not received a previous treatment targeting the ATR/CHK1 pathway

          -  Discontinued all previous treatments for cancer for at least 21 days or 5 half-lives,
             whichever is shorter, and recovered from the acute effects of therapy to CTCAE Grade
             ≤1. Palliative radiotherapy must have completed 1 week prior to start of study
             treatment.

          -  If patients have a germline BRCA mutation or a cancer with a somatic BRCA mutations or
             which is HRD positive and for which there is an approved PARP inhibitor, participants
             should have received such treatment before participating in the study unless
             contra-indicated

          -  At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can
             be assessed at baseline and is suitable for repeated radiological evaluation by RECIST
             v1.1 or Prostate Cancer Working Group-3 Guidelines (PCWG-3)

          -  Acceptable hematologic, renal, hepatic, and coagulation functions independent of
             transfusions and granulocyte colony-stimulating factor

          -  Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor
             lesion) available for submission for analysis via immunohistochemistry (IHC) for loss
             of ATM protein

          -  Female patients of childbearing potential and male patients with female partners of
             childbearing potential are required to use highly effective contraception

          -  Estimated life expectancy of ≥12 weeks

          -  Reliable and willing to make themselves available for the duration of the study and
             are willing to follow study procedures

        Additional inclusion criteria for participants in dose escalation (Part A1):

          -  Advanced or metastatic cancer which is refractory to standard therapies, or for which
             no standard therapies exist, or for which the investigator feels no other active
             therapy is required for the duration of the study

          -  Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale

        Additional inclusion criteria for participants in dose escalation (Part A2):

          -  Advanced or metastatic cancer for which gemcitabine is an appropriate treatment. Prior
             treatment with gemcitabine is permitted.

          -  Performance status of 0-2 on the ECOG scale

        Additional inclusion criteria for participants in dose expansion (Part B1):

          -  Patients with advanced or metastatic solid tumors with loss of ATM protein by IHC

          -  Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1

          -  Performance status of 0-2 on the ECOG scale

        Additional inclusion criteria for participants in dose expansion (Part B2):

          -  Females with histologically-confirmed diagnosis of high grade serous carcinoma of the
             ovary, fallopian tube or primary peritoneum that is not amenable to curative therapy

          -  Platinum-resistant disease, defined as disease progression within 6 months of last
             receipt of platinum-based chemotherapy. Patients must not have had primary
             platinum-refractory disease (disease that progressed during first-line or second-line
             platinum-based therapy).

          -  No more than one prior regimen in the platinum-resistant setting. Hormonal therapies
             and antiangiogenic therapies (as single agents) and PARP inhibitors used as
             maintenance therapy are not considered as separate lines of therapy. Patients should
             have previously received bevacizumab and chemotherapy unless contra-indicated.

          -  Have not received prior treatment with gemcitabine unless administered in combination
             with a platinum with no disease progression within 12 months after completion of that
             regimen

          -  Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1

          -  Performance status of 0-1 on the on the ECOG scale

        General Exclusion Criteria:

          -  Women who are pregnant, breast feeding, or who plan to become pregnant while in the
             study or within 4 weeks after the last administration of study treatment

          -  Men who plan to father a child while in the study or within 16 weeks after the last
             administration of study treatment

          -  Serious concomitant systemic disorder that would compromise the participants ability
             to adhere to the protocol including: one or more opportunistic HIV/AIDs-related
             infections within the past 12 months, hepatitis B virus, or hepatitis C virus; known
             history of clinical diagnosis of tuberculosis; malignancy prior to the one currently
             being treated that is not in remission

          -  Evidence of interstitial lung disease or pneumonitis (whether symptomatic or
             asymptomatic)

          -  Moderate or severe cardiovascular disease

          -  Valvulopathy that is severe, moderate, or deemed clinically significant

          -  Documented major electrocardiogram (ECG) abnormalities which are clinically
             significant

          -  Symptomatic or uncontrolled brain metastases, spinal cord compression, or
             leptomeningeal disease requiring concurrent treatment

          -  Received a live vaccine within 30 days before the first dose of study treatment

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the study, interfere with the patient's participation
             for the full duration of the study, or is not in the best interest of the patient to
             participate

          -  Recent major surgery within 4 weeks prior to entry into the study or minor surgery
             within 1 week of entry into the study

          -  Significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within
             12 weeks prior to enrollment

          -  Currently enrolled in a clinical trial involving an investigational product or any
             other type of medical research judged not to be scientifically or medically compatible
             with this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities (DLTs) from ART0380 monotherapy and in combination with gemcitabine
Time Frame:23 days (Cycle 0 Day -2 to Cycle 1 Day 21)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part B2: Number of participants with adverse events following administration of ART0380 in combination with gemcitabine or gemcitabine alone
Time Frame:From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380 or gemcitabine. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Pharmacokinetic Analysis (single dose): determine the plasma concentration of ART0380 when given alone and in combination with gemcitabine
Time Frame:PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Pharmacokinetic Analysis (multiple dose): determine the plasma concentration of ART0380 when given alone and in combination with gemcitabine
Time Frame:PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Pharmacokinetic Analysis: Renal clearance of ART0380
Time Frame:Urine PK will be measured during Cycle 1. Cycle 1 is 21 days.
Safety Issue:
Description:
Measure:Parts A1, B1, and B2: Objective response rate based on RECIST 1.1
Time Frame:Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Parts A1, B1, and B2: Duration of response based on RECIST 1.1
Time Frame:Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Parts A1 and B1: Progression free survival based on RECIST 1.1
Time Frame:Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Assess tumor biopsies by immunohistochemistry (IHC) for loss of Ataxia Telangiectasia Mutated (ATM) protein
Time Frame:Prior to dosing on Cycle 1 Day 1
Safety Issue:
Description:Where available archival tumor samples will be obtained for analysis of loss of ATM protein by IHC. If an archival tumor sample is not available, a pre-dose tumor biopsy must be taken.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Artios Pharma Ltd

Trial Keywords

  • Loss of Ataxia Telangiectasia Mutated (ATM) protein

Last Updated

April 8, 2021