ADRX-0405 for Solid Tumors

Recruiting at 7 trial locations

Overseen By Adcentrx Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adcentrx Therapeutics

Must not be taking: Anticancer, Investigational, Radiopharmaceuticals

Disqualifiers: CNS metastases, Cardiovascular disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ADRX-0405 to determine its safety and effectiveness for individuals with certain advanced cancers. The main goal is to identify the highest dose patients can tolerate without serious side effects. The trial targets cancers such as prostate cancer that no longer respond to standard treatments, as well as advanced gastric and lung cancers. Individuals diagnosed with these specific cancers may be suitable candidates for the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticancer or investigational therapy at least 14 days before starting, or 4 weeks for certain prostate cancer treatments. Routine antimicrobial prophylaxis is allowed, but active infection treatments are not.

Is there any evidence suggesting that ADRX-0405 is likely to be safe for humans?

Research has shown that ADRX-0405 appears promising in early lab studies. Animals tolerated it well, with no serious side effects reported. These initial studies suggest the drug is safe and effective against various tumors.

However, studies in humans are still ongoing. Some side effects have emerged during these trials. For instance, ADRX-0405 can decrease white blood cells, which are crucial for the immune system. Researchers continue to study the exact effects on humans.

In this early trial phase, researchers focus on understanding how the drug works in the body and its safety. This phase is crucial for determining the best dose that balances effectiveness and safety. While the treatment shows potential, more information from these human studies will help clarify its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which often include chemotherapy or targeted therapies, ADRX-0405 is unique because it focuses on a novel mechanism that targets specific tumor pathways. Researchers are excited about this treatment because it aims to selectively attack cancer cells with potentially fewer side effects than traditional chemotherapy. Additionally, ADRX-0405 might overcome resistance issues seen with current therapies, offering new hope for patients whose tumors have stopped responding to existing options.

What evidence suggests that ADRX-0405 might be an effective treatment for solid tumors?

Research has shown that ADRX-0405 is promising in early lab studies, performing well across various tumor types. These studies suggest it might target and treat solid tumors by delivering medicine directly to cancer cells. The treatment has demonstrated favorable absorption and elimination rates in the body. Although human studies provide limited information, early results indicate that ADRX-0405 could help treat advanced solid tumors. This trial includes a Phase 1a Dose Escalation arm to identify the maximum tolerated dose and a Phase 1b Dose Expansion arm to further evaluate its effectiveness in subjects with previously treated mCRPC. More detailed information is expected as ongoing trials continue. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with certain advanced solid tumors. Specific eligibility criteria are not provided, but typically participants must have a measurable disease that has progressed after treatment, be in good physical condition, and have no other medical issues that could interfere with the study.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

My prostate cancer is resistant to standard treatments and my testosterone levels are low.

I have advanced cancer, such as prostate, stomach, or lung cancer.

Exclusion Criteria

I have had lung inflammation needing steroids in the last 2 years or currently have it.

I am currently on medication for an active infection.

I have not had any other cancer than the current one in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Dose Escalation

Increasing doses of ADRX-0405 will be administered to identify the maximum tolerated dose (MTD) and the recommended dose for Phase 1b

Estimated 6 months

Phase 1b Dose Expansion

ADRX-0405 will be administered at the recommended dose from Phase 1a to evaluate safety, tolerability, and preliminary efficacy in subjects with previously treated mCRPC

Estimated 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADRX-0405

Trial Overview

The focus of this trial is ADRX-0405. Researchers want to find out how safe it is, what side effects it might cause, how the body processes it, and determine the best dose for patients with specific types of advanced solid tumors.

How Is the Trial Designed?

Group I: Phase 1b Dose Expansion Experimental Treatment 1 Intervention

ADRX-0405 will be initially administered at the dose recommended from the Phase 1a part in subjects with previously treated mCRPC.

Group II: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

Increasing doses of ADRX-0405 will be administered to identify the maximum tolerated dose (MTD) and the recommended dose to be used in the Phase 1b part.

ADRX-0405 is already approved in United States for the following indications:

Approved in United States as ADRX-0405 for:

• None approved; currently in Phase 1a/b clinical trial for advanced solid tumors

Who Is Running the Clinical Trial?

Adcentrx Therapeutics

Lead Sponsor

Trials

2

Recruited

210+

Published Research Related to This Trial

4-Demethoxydaunorubicin (4-DMDR) was tested in 32 patients with metastatic non-small cell lung cancer, showing only marginal activity with a major response rate of 3.3%, indicating limited efficacy at the studied dose of 40-50 mg/m2 every 21 days.

The most common side effect observed was leukopenia occurring 10-14 days after treatment, suggesting that while 4-DMDR may have less cardiotoxicity than daunorubicin, its overall therapeutic benefit in this patient population is minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of oral 4-demethoxydaunorubicin in patients with non-small cell lung cancer. Kris, MG., Gralla, RJ., Kelsen, DP., et al.[2019]

In a phase I trial involving 16 adult patients with solid tumors, the new drug 4-demethoxydaunorubicin was found to have a maximum tolerated dose of 18 mg/m2, with myelosuppression, particularly leucopenia, being the main dose-limiting side effect.

The study suggests that a starting dose of 15 mg/m2 every 3-4 weeks is appropriate for future phase II trials, indicating a potential for further investigation into its efficacy and safety in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of 4-demethoxydaunorubicin with single i.v. doses. Kaplan, S., Martini, A., Varini, M., et al.[2019]

In a study of 13,917 cancer patients, 297 hazardous drug-drug interactions (DDIs) were identified, with proton pump inhibitors (PPIs), dexamethasone, and fluoroquinolones being the most common culprits affecting oral antineoplastic agents (OAAs).

The research highlighted that younger patients, those taking multiple medications, and those on targeted therapies are at a higher risk for these hazardous DDIs, emphasizing the need for careful monitoring by healthcare providers when prescribing OAAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentially Hazardous Drug-Drug Interactions Associated With Oral Antineoplastic Agents Prescribed in Chinese Tertiary Care Teaching Hospital Settings: A Multicenter Cross-Sectional Study. Wang, H., Shi, H., Wang, Y., et al.[2022]

Patients with small-cell lung cancer (SCLC) had significantly higher pre-treatment levels of soluble death receptor 5 (sDR5) compared to healthy controls, indicating a potential biomarker for the disease.

Post-treatment levels of sDR5 decreased significantly after first-line chemotherapy and were strongly correlated with treatment responses and overall survival, suggesting that sDR5 could be used to predict patient outcomes in SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of serum soluble DR5 levels in small-cell lung cancer. Wan, Z., Zhang, X., Yu, X., et al.[2020]

Human osteosarcoma cells developed resistance to adriamycin (ADR) after repeated high-dose exposure, showing cross-resistance to other drugs like methotrexate and vincristine, but also collateral sensitivity to cisplatin.

Combining ADR treatment with verapamil, a calcium antagonist, enhanced the inhibition of growth in ADR-resistant osteosarcoma cells, suggesting a potential strategy to overcome drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug resistance and cross-sensitivity in cultured human osteosarcoma cells. Tomita, K., Kontani, T., Tsuchiya, H., et al.[2015]

In a study involving 16 patients with metastatic ovarian cancer, treatment with 4'deoxydoxorubicin at a dose of 30 mg/m2 every 3 weeks resulted in no clinical responses, indicating it is ineffective for this patient group.

The treatment was associated with infrequent toxicities, primarily neutropenia and thrombocytopenia, but overall, the lack of efficacy led to the conclusion that further investigation of 4'deoxydoxorubicin in this context is not warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of esorubicin (4'deoxydoxorubicin) in anthracycline naive patients with ovarian cancer. Green, MD., Speyer, JL., Wernz, JC., et al.[2019]

In a study involving 17 patients with advanced gastric adenocarcinoma, 4'-deoxydoxorubicin (DxDx) showed limited efficacy, with only one patient achieving a partial response lasting 2.5 months.

The treatment was associated with significant side effects, including severe myelosuppression in 69% of patients, leading to dose reductions, and a median survival of only 3.3 months after starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of 4'-deoxydoxorubicin (esorubicin) in advanced or metastatic adenocarcinoma of the stomach. Somlo, G., Doroshow, J., Akman, S., et al.[2019]

In a study of 16 patients with advanced small cell lung cancer, 4-Demethoxydaunorubicin (4-DMDNR) did not lead to complete or partial responses, but 9 patients experienced minor radiographic improvements and 6 reported transient symptomatic relief.

The treatment was generally well-tolerated with mostly minor side effects, and importantly, there was no evidence of cardiotoxicity; however, one patient did experience severe neutropenia leading to septicaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical and pharmacological study of oral 4-demethoxydaunorubicin in advanced non-pretreated small cell lung cancer. Milroy, R., Cummings, J., Kaye, SB., et al.[2019]

In a phase II study involving 18 patients with non-small cell lung cancer, the oral treatment with 4-demethoxydaunorubicin resulted in significant hematologic toxicity, with eight patients experiencing severe side effects (ECOG grade 3 or 4).

Despite the observed toxicity, there were no responses to the treatment, indicating that 4-demethoxydaunorubicin may not be effective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral 4-demethoxydaunorubicin (idarubicin) in bronchogenic lung cancer; phase II trial. Hochster, HS., Green, MD., Blum, RH., et al.[2019]

4'-Epi-doxorubicin (4'-epi-DX) combined with cis-dichlorodiammineplatinum (CDDP) showed promising efficacy in treating advanced solid tumors, with complete remission in 5 patients and partial remission in 12 out of 52 evaluable patients, particularly in ovarian and lung cancers.

The treatment was well-tolerated, with mild to moderate hematologic toxicity and no observed cardiac toxicity, making it a safer alternative to traditional doxorubicin, which is known for its higher toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of 4'-epi-doxorubicin plus cis-platinum in advanced solid tumors. Martoni, A., Tomasi, L., Farabegoli, G., et al.[2019]

The anti-DR5 antibody DS-8273a shows high immunoreactivity and strong binding affinity to DR5-expressing cancer cells, indicating its potential effectiveness in targeting tumors for treatment.

Radiolabeled versions of DS-8273a demonstrated specific uptake in tumor models without affecting normal tissues, suggesting that it can be used as a novel PET imaging agent to assess drug delivery and patient response in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Evaluation of 89Zr-DS-8273a as a Theranostic for Anti-Death Receptor 5 Therapy. Burvenich, IJ., Lee, FT., Guo, N., et al.[2018]

In a phase I trial involving 51 adults with advanced gastrointestinal solid tumors, 4-demethoxydaunorubicin (4-dm DNR) was safely administered in oral capsules, with no fatal toxicity observed at doses up to 25.0 mg/m2.

However, dose-limiting granulocytopenia and non-hematologic toxicity occurred at doses of 22.5 mg/m2 or higher, and no therapeutic responses were recorded, indicating limited efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of 4-demethoxydaunorubicin by oral route in patients with advanced cancer. Krarup-Hansen, A., Andersen, E., Elbaek, K., et al.[2019]

In a phase I study involving 22 patients with advanced solid tumors, 4'-epi-Adriamycin (4'-epi-ADM) showed a similar toxicity profile to Adriamycin but with reduced side effects like vomiting, hair loss, and bone marrow suppression.

Two patients experienced objective improvements in their conditions, suggesting that 4'-epi-ADM may be effective, warranting further clinical studies to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary phase I study of 4'-epi-adriamycin. Bonfante, V., Bonadonna, G., Villani, F., et al.[2013]

The engineered single-chain variable fragment (aDR5scFv) specifically targets and induces apoptosis in human lung adenocarcinoma cells, demonstrating its potential as a cancer treatment.

In addition to effectively killing cancer cells in vitro, aDR5scFv also inhibited tumor growth in mice, suggesting it could be a promising therapeutic candidate, especially when combined with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of aDR5scFv with Specific Identification and Function. Cheng, X., Meng, Q., Gao, C., et al.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06710379

NCT06710379 | A Study of ADRX-0405 in Subjects With ...

The primary purpose of this study is to assess the safety, tolerability, and pharmacokinetics, and to identify the optimal dose of ADRX-0405 in patients with ...

2.

adcentrx.com

adcentrx.com/adcentrx-therapeutics-doses-first-patient-in-phase-1a-with-adrx-0405-steap1-adc/

Adcentrx Therapeutics Announces First Patient Dosed in ...

The first-in-human Phase 1a/b clinical trial of ADRX-0405 is an open-label dose escalation and dose expansion study being conducted across sites ...

3.

onclive.com

onclive.com/view/fda-grants-orphan-drug-designation-to-adrx-0405-for-gastric-cancer

FDA Grants Orphan Drug Designation to ADRX-0405 for ...

The phase 1a/b trial is evaluating ADRX-0405's safety, tolerability, pharmacokinetics, and optimal dose in patients with advanced solid tumors.

4.

targetedonc.com

targetedonc.com/view/fda-clears-ind-of-adrx-0405-next-gen-adc-in-solid-tumors

FDA Clears IND of ADRX-0405, Next-Gen ADC, in Solid ...

In preclinical studies, ADRX-0405 has demonstrated promising pharmacokinetics, safety, and efficacy in multiple tumor models. ADRX-0405 is ...

5.

cancernetwork.com

cancernetwork.com/view/fda-grants-orphan-drug-designation-to-adrx-0405-for-gastric-cancer

FDA Grants Orphan Drug Designation to ADRX-0405 for ...

Results from the phase 1a/b trial evaluating ADRX-0405 in various solid tumors, including gastric cancer, are expected to come in late 2025.

6.

adcentrx.com

adcentrx.com/adcentrx-adrx-0405-ind-clearance/

Adcentrx Therapeutics Announces FDA Clearance of ...

ADRX-0405 preclinical studies have demonstrated its favorable pharmacokinetics, safety profile, and significant efficacy across multiple tumor ...

7.

withpower.com

withpower.com/trial/adrx-0405-for-solid-tumors-658cb

ADRX-0405 for Solid Tumors

The safety data for ADRX-0405, evaluated under different names, shows that at certain doses, it can cause side effects like granulocytopenia (low white ...

8.

aacrjournals.org

aacrjournals.org/cancerres/article/85/8_Supplement_1/1159/754922/Abstract-1159-Preclinical-characterization-of-a

Abstract 1159: Preclinical characterization of a novel STEAP1 ...

Consequently, ADRX-0405 was well tolerated in non-human primates repeat-dose toxicology evaluation. Strikingly, no toxicity was detected in the ...