Treatment with ATR Inhibitor for Advanced or Metastatic Solid Tumors

About the Study

This study will look at how well a new oral targeted therapy known as an ATR inhibitor works on advanced or metastatic solid tumors with mutations in genes linked to DNA damage repair. The study will look at response to treatment with the drug ART0380 either alone or in combination with the chemotherapy agent, gemcitabine. 

Type of Study

This is an open-label, non-randomized study.

• All participants will receive the study drug ART0380 either alone or in combination with gemcitabine. 
• All participants will know which medication they are receiving.
• The study will have different groups of participants. Participants will be assigned to a group based on type of cancer, tumor testing and/or genetic testing.
  • the dose escalation groups will establish the ideal dose of ART0380.
  • the dose expansion groups will include additional patient populations. 

Participant groups:

• Group A1 - People with advanced or metastatic cancer that is not responsive to standard therapies, or for which no standard therapies exist.
• Group A2 - People with advanced or metastatic cancer for whom gemcitabine is appropriate treatment. 
• Group B1 - People with advanced or metastatic cancer whose tumor shows a loss of the ATM protein.
• Group B2 - People diagnosed with advanced, platinum-resistant ovarian cancer. 

What the Study Entails:

All participants in this study will receive ART0380 orally either intermittently (once daily 3 days on, 4 days off or days 2-4 and 9-11) or continuously (once daily each day) in 21 day cycles. 

Group A1

• Participants will receive ART0380 orally either intermittently (once daily 3 days on, 4 days off or days 2-4 and 9-11) or continuously (once daily each day) in 21 day cycles.

Group A2

• Participants will receive ART0380 orally either intermittently (once daily 3 days on, 4 days off or days 2-4 and 9-11) or continuously (once daily each day) in 21 day cycles.
• Participants will also receive gemcitabine on Days 1 and 8 of a 21 day cycle.

Group B1

• Participants will receive ART0380 orally either intermittently (once daily 3 days on, 4 days off or days 2-4 and 9-11) or continuously (once daily each day) in 21 day cycles.

Group B2 

• Participants will receive ART0380 orally either intermittently (once daily 3 days on, 4 days off or days 2-4 and 9-11) or continuously (once daily each day) in 21 day cycles.
• Participants will also receive gemcitabine on Days 1 and 8 of a 21 day cycle.

All study participants will be followed for up to 24 months.

Study Sites

Colorado
Denver, Colorado
Sarah Cannon Research Institute at HealthONE 
Principal Investigator: Gerald Falchook, MD
[email protected]
844-710-6157

Florida
Orlando, Florida
Florida Cancer Specialists 
Principal Investigator: Cesar Perez, MD
[email protected]
844-710-6157     

Sarasota, FL
Florida Cancer Specialists
Principal Investigator: Manish Patel, MD
[email protected]
844-710-6157         

Oklahoma
Oklahoma City, OK
Stephenson Cancer Center      
Principal Investigator: Kathleen Moore, MD
[email protected]
844-710-6157            

Tennessee
Nashville, TN
Tennessee Oncology
Principal Investigator: Melissa Johnson, MD
[email protected]
844-710-6157             

People may be eligible if they:

• Have not received a previous treatment targeting the ATR/CHK1 pathway (this includes other ATR inhibitors, CHK1 inhibitors and WEE1 inhibitors). 
• For participants with an inherited or somatic BRCA mutation, or a tumor that is HRD positive and for which there is an approved PARP inhibitor, they should have received PARP inhibitor treatment before participating in this study. 
• Have at least one tissue sample that can be followed by imaging at time of study enrollment and during future evaluations.
• Have tumor tissue samples that can be tested for loss of ATM protein.

Additional inclusion criteria for participants in Group A1:

• Advanced or metastatic cancer that is not responsive to standard therapies, or for which no standard therapies exist

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

• Advanced or metastatic cancer for which gemcitabine is appropriate treatment. 

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

• Advanced or metastatic cancer in which tumor testing shows a  loss of ATM protein.

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

• Advanced platinum-resistant ovarian, fallopian tube or primary peritoneal cancer that is not responsive to curative therapy.
• No more than one prior treatment in the platinum-resistant setting. Must have previously received bevacuzimab and chemotherapy.
• Have not received prior treatment with gemcitabine unless administered in combination with a platinum, and no disease progression after 12 months.

People with the following are not eligible for the study:

• Have recent HIV/AIDs-related infections, hepatitis B or hepatitis C, tuberculosis, an existing additional malignancy that is not in remission.
• Lung disease or pneumonitis.
• Moderate or severe heart disease.
• Brain metastases, spinal cord compression, or leptomeningeal disease (cancer cells that have migrated to the fluid around the brain and spinal cord) requiring treatment at the same time as this study.