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

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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

• 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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Artios Pharma Ltd
• Treatments: Gemcitabine

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