ARTS-021 for Advanced Cancer

Recruiting at 12 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Avenzo Therapeutics, Inc.

Must not be taking: CDK2 inhibitors, PKMYT1 inhibitors

Disqualifiers: Active CNS metastases, Unstable cardiac, others

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

Compensation: Varies

Number of Visits: 56

430 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of a new oral medication, ARTS-021 (also known as AVZO-021), for treating advanced solid tumors. It specifically targets tumors resistant to other treatments, such as certain types of breast and ovarian cancers. ARTS-021 inhibits a protein called CDK 2, which plays a role in cancer cell growth. Suitable candidates for this trial have advanced cancer unresponsive to standard treatments and must be able to swallow capsules or tablets. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong or moderate CYP3A4 inhibitors or inducers before starting the study medication. If you're on these types of medications, you may need to discuss alternatives with your doctor.

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

Research shows that AVZO-021, also known as ARTS-021, is being tested for safety and effectiveness in treating advanced solid tumors. This marks the first use of this treatment in humans, prompting researchers to closely monitor patient responses.

Currently, no specific safety information from these human trials is available. As the trial is in its early stages, researchers focus on determining the right dose and observing any side effects. They continue to assess its safety.

This treatment targets a protein called CDK2, which aids cell growth. Earlier studies in the lab or on animals indicated that AVZO-021 might effectively stop tumor growth. However, without human data, it remains too early to determine its safety or tolerance, which remains a primary focus of ongoing research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ARTS-021 for advanced cancer because of its novel approach to treatment. Unlike current cancer therapies that often involve intravenous administration, ARTS-021 is an oral medication, making it potentially more convenient for patients. It also targets cancer cells differently by incorporating AVZO-021, which may enhance its effectiveness either alone or in combination with other cancer drugs like fulvestrant, palbociclib, or carboplatin. This innovative strategy could offer new hope for patients with advanced cancer by potentially improving outcomes and reducing side effects compared to traditional treatments.

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

Research shows that AVZO-021 is a promising treatment for advanced solid tumors. This oral medication blocks cyclin-dependent kinase 2 (CDK2), an enzyme that aids cancer cell growth. Studies have found that AVZO-021 effectively targets CDK2, preferring it over the similar enzyme CDK1 by more than 600 times. Early results suggest it could be particularly beneficial for cancers with a genetic change called cyclin E1 (CCNE1) amplification, which accelerates tumor growth. In this trial, researchers are testing AVZO-021 both as a monotherapy and in combination with other cancer drugs, such as fulvestrant and palbociclib, to assess its potential to enhance their effectiveness. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Adults (18+) with advanced solid tumors where standard treatments are ineffective, inappropriate, or unsafe. Participants must have measurable disease, not be pregnant or breastfeeding, and agree to use effective birth control. They should be in good physical condition (ECOG 0-1) with proper organ function and able to take oral medication.

Inclusion Criteria

My liver, kidneys, blood, and clotting functions are all working well.

I am fully active or can carry out light work.

Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 6 months following the last dose of study treatment

Exclusion Criteria

I had major surgery less than 4 weeks before starting ARTS-021.

I haven't had a heart attack or significant heart disease in the last 6 months.

I have not taken steroids or had immunodeficiency issues in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose-escalation phase to assess safety and tolerability of AVZO-021 and determine the recommended phase 2 dose (RP2D) as monotherapy and combination therapy

Approximately 16 months

28-day cycles

Phase 2 Treatment

Dose-expansion phase to assess the antitumor activity of AVZO-021 as monotherapy and combination therapy

Approximately 52 months

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 76 months

What Are the Treatments Tested in This Trial?

Interventions

• ARTS-021

Trial Overview

The trial is testing ARTS-021's safety and effectiveness against advanced solid tumors. It involves different phases: monotherapy dose escalation for various cancers; combination dose expansion for specific breast cancer types and ovarian cancer; both using additional drugs like Palbociclib.

How Is the Trial Designed?

Group I: Phase 2, monotherapy (Part 2A) Experimental Treatment 1 Intervention

Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Part 1A.

Group II: Phase 2, combination (Parts 2B and 2C) Experimental Treatment 8 Interventions

Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Parts 1B/1C, in combination with: 2B1) fulvestrant 2B2) palbociclib plus either fulvestrant or letrozole 2B3) ribociclib plus either fulvestrant or letrozole 2B4) abemaciclib plus either fulvestrant or letrozole 2B5) sacituzumab govitecan-hziy 2C) carboplatin

Group III: Phase 1, monotherapy (Part 1A) Experimental Treatment 1 Intervention

Escalating doses of once daily, oral AVZO-021 in 28-day cycles.

Group IV: Phase 1, combination (Parts 1B and 1C) Experimental Treatment 8 Interventions

Escalating doses of once daily, oral AVZO-021 in 28-day cycles starting at least 1 DL below the monotherapy MTD/RP2D dose in combination with: 1B1) fulvestrant 1B2) palbociclib plus either fulvestrant or letrozole 1B3) ribociclib plus either fulvestrant or letrozole 1B4) abemaciclib plus either fulvestrant or letrozole 1B5) sacituzumab govitecan-hziy 1C) carboplatin

Who Is Running the Clinical Trial?

Avenzo Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

430+

Allorion Therapeutics Inc

Lead Sponsor

Trials

2

Recruited

510+

Published Research Related to This Trial

Patients with advanced non-small-cell lung cancer who have a performance status of 2 (PS2) are often excluded from clinical trials, leading to a lack of data to inform treatment decisions for this group.

While single-agent chemotherapy is still the standard treatment for PS2 patients, emerging evidence suggests that new agents or combination therapies may be beneficial, highlighting the need for a large Phase III trial to compare these treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of performance status 2 patients with advanced non-small-cell lung cancer: what we know and what we don't know. Tartarone, A., Aieta, M.[2009]

In a study of 612 patients with advanced non-small-cell lung cancer (NSCLC), those with a performance status (PS) of 0-1 showed a significant survival benefit from cisplatin combination therapy, with a median survival of 43 weeks compared to lower survival rates for other treatments.

Patients with a performance status of 2 did not experience any survival advantage from cisplatin combination therapy, indicating that this treatment may not be effective for those with poorer health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do all patients with advanced non-small-cell lung cancer benefit from cisplatin-based combination therapy? Soria, JC., Brisgand, D., Le Chevalier, T.[2020]

Patients with advanced non-small cell lung cancer (NSCLC) and a poor performance status (PS2) generally have worse outcomes compared to those with better performance statuses (PS0-1), as shown in a review of ten studies.

In a phase 3 study, PS2 patients receiving a combination of pemetrexed and carboplatin showed improved overall survival and progression-free survival compared to those receiving only pemetrexed, suggesting that this combination may be beneficial despite not being an approved treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review). Zinner, R., Visseren-Grul, C., Spigel, DR., et al.[2023]

Chemotherapy has been shown to improve survival and quality of life in patients with advanced non-small cell lung cancer, including those with poor performance status (PS2), who historically have been underrepresented in clinical trials.

Recent studies indicate that PS2 patients can benefit from chemotherapy, with combination treatments like carboplatin and paclitaxel potentially offering better outcomes than single-agent therapies, without significantly increased toxicity compared to fitter patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. Langer, C., Lilenbaum, R.[2019]

In a study of 48 patients with advanced non-small-cell lung cancer (NSCLC), the combination of paclitaxel and carboplatin resulted in a 37.5% objective response rate, indicating its effectiveness in treating this condition.

The treatment was generally well-tolerated, with the most common side effects being bone marrow suppression, nausea/vomiting, and hair loss, and it was found to be more effective in patients who had not previously received treatment compared to those who had.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitacxel and carboplatin in advanced non-small-cell lung cancer. Huang, PW., Gu, YH., Lu, KH., et al.[2015]

Citations

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clinicaltrials.gov/study/NCT05867251

Study of AVZO-021 in Patients With Advanced Solid Tumors

AVZO-021 is a compound being developed for the treatment of patients with advanced solid tumors, specifically, HR+/HER2- breast cancer and cyclin E1 (CCNE1) ...

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clin.larvol.com

clin.larvol.com/trial-detail/NCT05867251

Study of AVZO-021 in Patients With Advanced Solid Tumors

A potentially best-in-class cyclin-dependent kinase 2 (CDK2) selective inhibitor being studied in an ongoing US-based Phase 1 clinical study for the treatment ...

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ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e17546

Phase 1/2 study of ARTS-021, a potent, oral administrated, ...

Taken together, these data support the clinical development of ARTS-021 as a monotherapy in CCNE1-amplified cancers and in combination with CDK4 ...

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annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)01905-7/pdf

439TiP AVZO-021-1001

Combination dose-escalation will be initiated with fulvestrant and current CDK4/6 inhibitors (Part 1b) in patients with HR+/HER2- mBC, and an additional ...

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withpower.com

withpower.com/trial/phase-2-neoplasms-6-2023-bcd3b

ARTS-021 for Advanced Cancer

Trial Overview The trial is testing ARTS-021's safety and effectiveness against advanced solid tumors. It involves different phases: monotherapy dose escalation ...

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annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)01905-7/fulltext

439TiP AVZO-021-1001: A first-in-human open-label ...

Preclinical data support AVZO-021 as a monotherapy in CCNE1-amplified cancers and in combination with CDK4/6i in HR+/HER2- BC. Additional combinations with ...

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avenzotx.com

avenzotx.com/press-releases/avenzo-therapeutics-announces-clinical-study-collaboration-with-gilead-sciences-to-evaluate-avzo-021-and-trodelvy-in-hr-her2-metastatic-breast-cancer/

Metastatic Breast Cancer

AVZO-021, a potential best-in-class CDK2 inhibitor, to be evaluated in combination with Trodelvy (sacituzumab govitecan-hziy), Gilead's Trop-2 directed ADC.

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centerwatch.com

centerwatch.com/clinical-trials/listings/NCT05867251/study-of-avzo-021-in-patients-with-advanced-solid-tumors

Study of AVZO-021 in Patients With Advanced Solid Tumors

This study, the first clinical trial of AVZO-021, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, ...