ART0380 for Advanced Cancer

Recruiting at 75 trial locations

Overseen By Minal Barve, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Artios Pharma Ltd

Must not be taking: UGT1A1 inhibitors

Disqualifiers: Pregnancy, HIV/AIDS, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles

502 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ART0380, to determine the optimal dose and assess its effectiveness on advanced cancers that have spread. The study examines ART0380 both alone and in combination with other cancer drugs like gemcitabine or irinotecan. It targets individuals with specific cancers, such as endometrial, colorectal, or pancreatic, who have not responded to standard treatments. For those with challenging cancers and limited options, this trial might be suitable. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop all previous cancer treatments for at least 21 days or 5 half-lives, whichever is shorter, before starting the study. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ART0380, whether used alone or with other drugs like irinotecan or gemcitabine, undergoes careful testing for safety in humans. Previous studies found that ART0380 is generally well-tolerated, meaning most people do not experience serious side effects. However, like any treatment, some side effects can occur.

For ART0380, some participants reported minor side effects, but these are usually manageable. Using ART0380 with irinotecan or gemcitabine does not appear to cause more severe side effects than using ART0380 alone. This suggests that the drug, whether used by itself or with other drugs, could be a safe option for people with advanced cancer, depending on further study results.

It is important to know that ART0380 is still in the early stages of testing, so researchers continue to learn about its complete safety profile. So far, evidence suggests it is a promising and relatively safe treatment option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ART0380 because it brings a fresh approach to cancer treatment. Unlike standard options like chemotherapy, which broadly targets rapidly dividing cells, ART0380 is a more targeted therapy. It’s designed to work on specific genetic alterations in cancer cells, such as those involving the ATM gene, which could make it more effective for certain tumors while potentially causing fewer side effects. ART0380 can be used alone or in combination with other drugs like irinotecan, offering flexibility in treatment plans. This precision targeting is what sets ART0380 apart and makes it a promising option in the fight against advanced cancers.

What evidence suggests that this trial's treatments could be effective?

Research has shown that ART0380, a drug tested for various cancers, shows promise due to its mechanism of action. ART0380 targets ATR kinase, a protein that aids cancer cells in repairing damaged DNA. By blocking this repair process, ART0380 may increase the likelihood of cancer cell damage and death. In this trial, participants with colorectal cancer receive ART0380 combined with irinotecan, and early results indicate that this combination is well-tolerated and effective. Additionally, ART0380 is being tested with gemcitabine in participants with ovarian cancer, and this combination has shown encouraging early results. Overall, these findings suggest that ART0380 might help treat certain advanced cancers by hindering cancer cell repair. ^{6 7 8 9 10}

Who Is on the Research Team?

Antonio Gonzalez, MD, PHD

Principal Investigator

Clinica Universidad de Navarra, Madrid

Susanna Ulahannan, MD

Principal Investigator

Oklahoma University

Kim Reiss Binder, MD

Principal Investigator

University of Pennsylvania / Abramson Cancer Center

Melissa Johnson, MD

Principal Investigator

Tennessee Oncology

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including specific types of ovarian, fallopian tube, and peritoneal cancers. Participants must have a measurable lesion, be in good physical condition (ECOG 0-1), not have had certain prior treatments or uncontrolled brain issues, and agree to use effective contraception.

Inclusion Criteria

I stopped all cancer treatments at least 21 days ago and have recovered from their immediate side effects.

I can take care of myself and perform daily activities.

I haven't been treated with gemcitabine alone for my condition.

Exclusion Criteria

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

I do not plan to father a child during the study or within 4 months after it ends.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ART0380 as monotherapy or in combination with gemcitabine or irinotecan in 21-day cycles

21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Progression free survival is assessed every 6 weeks for 18 weeks, then every 9 weeks up to approximately 24 months

24 months

What Are the Treatments Tested in This Trial?

Interventions

• ART0380

Trial Overview The study tests ART0380 alone and alongside gemcitabine or irinotecan to determine the safest dose, understand side effects better, and evaluate effectiveness against these cancers. It involves patients who've had no luck with standard therapies or those without existing options.

How Is the Trial Designed?

Group I: Part B7 Experimental Treatment 2 Interventions

In Part B7, participants with colorectal cancer (CRC) will receive ART0380 in combination with irinotecan on a 21-day cycle.

Group II: Part B6 Experimental Treatment 2 Interventions

In Part B6, participants with pancreatic ductal adenocarcinoma (PDAC) or acinar cell carcinoma will receive ART0380 in combination with irinotecan on a 21-day cycle.

Group III: Part B5 Experimental Treatment 2 Interventions

In Part B5, participants with colorectal cancer (CRC) will receive ART0380 in combination with irinotecan on a 21-day cycle.

Group IV: Part B4 Experimental Treatment 1 Intervention

In Part B4, participants with advanced or metastatic solid tumors received ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

Group V: Part B3 Experimental Treatment 1 Intervention

in Part B3, participants with persistent or recurrent endometrial cancer (EC) received ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

Group VI: Part B2 Experimental Treatment 2 Interventions

In Part B2, participants with high grade serous ovarian, primary peritoneal, or fallopian tube carcinoma were randomized (open label) 1:1 to either ART0380 in combination with gemcitabine or gemcitabine alone.

Group VII: Part B1 Experimental Treatment 3 Interventions

In Part B1, up to 7 cohorts enrolled participants with solid cancers with alterations in the ATM (ataxia-telangiectasia mutated) gene likely to predict for loss of ATM protein will be treated with either * ART0380 monotherapy Or * ART0380 in combination with irinotecan

Group VIII: Part A3 Fed/Fast Experimental Treatment 2 Interventions

Part A3 Fed/Fast will evaluate intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles in a fasting or fed state.

Group IX: Part A3 Experimental Treatment 2 Interventions

Part A3 evaluated intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles.

Group X: Part A2 Experimental Treatment 2 Interventions

Part A2 evaluated intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles.

Group XI: Part A1 Experimental Treatment 1 Intervention

Part A1 evaluated intermittent and continuous dosing of ART0380 monotherapy. Treatment was given in 21-day cycles.

Who Is Running the Clinical Trial?

Artios Pharma Ltd

Lead Sponsor

Trials

6

Recruited

1,600+

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02703-5/fulltext

680P First results from the phase I trial of the ATR inhibitor, ... Patients (pts) with advanced solid cancers received escalating doses of ART0380 on a continuous daily (QD) or intermittent (3 days on, 4 days off) schedule.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04657068

NCT04657068 | A Study of ART0380 for the Treatment ... 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 ...

3. artios.com artios.com/wp-content/uploads/2023/11/ART0380-ESMO-Poster-2023.pdf

ART0380-ESMO-Poster-2023.pdf ART0380 induced DNA damage as shown by increased γH2Ax in CTCs from patients whose tumor harbored a. DDR deficiency. There was no trend of increasing γH2Ax in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05798611

Study of ART0380 in Patients With Biologically Selected ... This interventional study will evaluate the efficacy and safety of ART0380 as monotherapy in patients whose tumors have a biology to predict for sensitivity to ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39630604/

Discovery of ART0380, a Potent and Selective ATR Kinase ... We describe the discovery and characterization of ART0380 (6), a potent and selective ATR inhibitor with a compelling in vitro and in vivo pharmacological ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04657068

NCT04657068 | A Study of ART0380 for the Treatment ... 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 ...

7. trials.braintumor.org trials.braintumor.org/trials/NCT04657068

A Study of ART0380 for the Treatment of Advanced or Metastatic ... 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04657068?term=AREA%5BConditionSearch%5D(Ataxia%20telangiectasia%20OR%20%22ataxia%20-%20telangiectasia%22%20OR%20%22%20ataxia%20telangiectasia%20syndrome%22%20OR%20%22%20boder-Sedgwick%20syndrome%22%20OR%20%22%20Louis%20Bar%20syndrome%22%20OR%20%22%20Louis-Bar%20syndrome%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=7

A Study of ART0380 for the Treatment of Advanced or ... 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 ...

9. cancer.gov cancer.gov/clinicaltrials/NCI-2021-04129

A Study of ART0380 for the Treatment of Advanced or ... 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: ...

10. dana-farber.org dana-farber.org/clinical-trials/23-205

A Phase II, Open-label, Multi-center, Basket Study of the ... This interventional study will evaluate the efficacy and safety of ART0380 as monotherapy in patients whose tumors have a biology to predict for sensitivity ...