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

  • STATUS
    Recruiting
  • End date
    Dec 2, 2023
  • participants needed
    232
  • sponsor
    Artios Pharma Ltd
Updated on 2 May 2022
cancer
measurable disease
carcinoma
colony stimulating factor
gm-csf
hormone therapy
gemcitabine
irinotecan
bevacizumab
g-csf
ATR
cancer chemotherapy
parp inhibitor
fallopian tube
platinum-based chemotherapy
ovarian epithelial carcinoma

Summary

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 or irinotecan
  • Learn more about the side effects of ART0380 alone and in combination with gemcitabine or irinotecan
  • Learn more about the effectiveness of ART0380 alone and in combination with gemcitabine or irinotecan

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 or irinotecan 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.

Details
Condition Advanced Cancer, Metastatic Cancer, Ovarian Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer
Treatment Gemcitabine, Irinotecan, ART0380
Clinical Study IdentifierNCT04657068
SponsorArtios Pharma Ltd
Last Modified on2 May 2022

Eligibility

Yes No Not Sure

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 known 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 plus one barrier method during their participation in the study and for 4 or 16 weeks respectively following the last dose. For male and female patients given gemcitabine or irinotecan, highly effective contraception plus one barrier method must be used from study entry until 6 months after the last dose of study treatment. Male patients are required to refrain from donating sperm during their participation in the study and for 6 months following last dose
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 escalation (Part A3)
Advanced or metastatic cancer for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted
Performance status of 0-1 on the ECOG scale
Additional inclusion criteria for participants in dose expansion (Part B1)
Patients with advanced or metastatic solid tumors with alterations to the ATM gene likely to predict for loss of ATM protein
Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
Additional inclusion criteria for participants in dose expansion (Part B2)
Performance status of 0-1 on the ECOG scale
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

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
Moderate or severe cardiovascular disease
Evidence of interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic). Patients with a previous history of these conditions which have resolved may be permitted to enter the study after discussion with the medical monitor (applicable to US population only)
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
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
Significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment
Additional exclusion criteria for participants in dose escalation (Part A3)
Patients who are homozygous for the UGT1A1 6 or 28. (UGT1A1 7/7 genotype), or simultaneously heterozygous for the UGT1A1 6 and 28. (UGT1A1 7/7 genotype)
Patients receiving inhibitors of UGT1A1 within 2 weeks before the first dose of study treatment
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