SQ3370 for Cancer

Recruiting at 11 trial locations

Overseen By Shasqi Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shasqi, Inc.

Must not be taking: Anthracyclines, Trastuzumab

Disqualifiers: Congestive heart failure, CNS metastases, 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, up to 2 years

145 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, and preliminary activity of SQ3370 in patients with advanced solid tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude those who have had certain treatments like chemotherapy or immunotherapy within 28 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug SQ3370 for cancer?

Research shows that doxorubicin prodrugs, like those used in SQ3370, have been developed to have greater anticancer activity and less toxicity compared to regular doxorubicin. Additionally, similar doxorubicin prodrugs have shown higher antitumoral efficacy in certain cancer models, suggesting potential effectiveness for SQ3370. ^{1 2 3 4 5}

Is SQ3370 safe for humans?

The safety of SQ3370, a doxorubicin prodrug, is supported by studies showing reduced toxicity compared to traditional doxorubicin, with improved safety profiles in animal models and clinical trials for similar prodrugs. These studies suggest that SQ3370 may be safer than standard doxorubicin, which is known for its severe side effects. ^{6 7 8 9 10}

What makes the drug SQ3370 unique compared to other cancer treatments?

SQ3370 is unique because it uses a prodrug form of doxorubicin that is activated specifically at the tumor site, potentially reducing side effects by limiting exposure to healthy tissues. This targeted approach aims to increase the concentration of the active drug in the tumor while minimizing its presence in other parts of the body, such as the heart, where doxorubicin can cause significant toxicity. ^{3 10 11 12 13}

Research Team

Jim Williams, MD

Principal Investigator

Shasqi, Inc.

Eligibility Criteria

This trial is for adults with advanced solid tumors where anthracyclines might help. They should be relatively fit (ECOG score 0-1), have a tumor that can be injected, and their body's blood-making, liver, kidney, and clotting functions should be good. People who've had lots of Dox or Epirubicin, heart issues, recent cancer treatments except certain kinase inhibitors, recent transfusions or are pregnant/breastfeeding can't join.

Inclusion Criteria

I have been diagnosed with advanced soft tissue sarcoma or another type of solid tumor.

My cancer type responds to a specific chemotherapy drug.

I am fully active or can carry out light work.

Exclusion Criteria

Pregnant or breast-feeding women.

I am allergic to Dox, hyaluronic acid, or certain bacterial proteins.

I do not have any uncontrolled health conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle and escalating doses of SQP33 protodrug administered IV from Day 1 through Day 5 of each cycle

21-day cycles, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• SQ3370

Trial Overview The study tests SQ3370's safety and early effectiveness in treating advanced solid tumors. It's an initial phase trial to see how patients tolerate the drug and if it shows any promise against these cancers.

Participant Groups

Group I: Phase 2a Expansion Group 3a (Head and Neck) Experimental Treatment 1 Intervention

Participants with histologically or cytologically confirmed relapsed or metastatic squamous-cell carcinoma of the head and neck, who have exhausted curative intent therapies or patients with distant metastases who may have received one or less chemotherapy regimen.

Group II: Phase 2a Expansion Group 2 (Unresectable STS) Experimental Treatment 1 Intervention

Locally advanced, unresectable or metastatic, soft tissue sarcomas who are anthracycline naïve.

Group III: Phase 2a Expansion Group 1 (Extremity STS) Experimental Treatment 1 Intervention

Participants with soft tissue sarcomas of the extremity AJCC Stage III OR IV (\>5 cm injectable tumors locally advanced and or metastatic, not amendable to primary surgical intervention and who are anthracycline naïve.

Group IV: Dose Escalation Cohort (20 mL SQL70) Experimental Treatment 1 Intervention

Participants will receive 20 mL of SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle into a single lesion and then receive escalating doses of SQP33 protodrug administered IV from Day 1 through Day 5 (5 doses) of each 21-day cycle.

Group V: Dose Escalation Cohort (10 mL SQL70) Experimental Treatment 1 Intervention

Participants will receive 10 mL of SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle into a single lesion and then receive escalating doses of SQP33 protodrug administered IV from Day 1 through Day 5 (5 doses) of each 21-day cycle.

Group VI: Cohort A Experimental Treatment 1 Intervention

Participants will receive SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle into a single lesion as determined in Dose Escalation. Then will receive a lower dose than RP2D of SQP33 protodrug administered IV from Day 1 through Day 5 (5 doses) of each 21-day cycle.

Who Is Running the Clinical Trial?

Shasqi, Inc.

Lead Sponsor

Trials

1

Recruited

150+

Findings from Research

The PSSN10 nanocarrier effectively co-delivers the immune checkpoint inhibitor NLG919 and the chemotherapeutic doxorubicin (DOX), enhancing drug accumulation in tumor tissues and promoting T-cell immune responses, leading to significant tumor growth inhibition in mice.

In comparison to standard treatments like DOXIL and free DOX, the DOX/PSSN10 micelles demonstrated superior efficacy in reducing tumor size and improving survival rates in 4T1.2 tumor-bearing mice, indicating a promising new approach for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier. Sun, JJ., Chen, YC., Huang, YX., et al.[2018]

ALGP-doxorubicin (ALGP-doxo) demonstrated significantly higher antitumoral efficacy compared to standard doxorubicin in patient-derived xenograft models of synovial sarcoma and dedifferentiated liposarcoma, leading to tumor shrinkage and stabilization.

The prodrug ALGP-doxo was well-tolerated at doses 30- to 40-fold higher than doxorubicin, with no significant adverse events reported, suggesting it may be a safer alternative for treating soft tissue sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Antitumoral Efficacy of PhAc-ALGP-Doxorubicin, an Enzyme-Activated Doxorubicin Prodrug, in Patient-Derived Soft Tissue Sarcoma Xenograft Models. Cornillie, J., Wozniak, A., Pokreisz, P., et al.[2020]

S9788, a new drug, can effectively reverse multidrug resistance in cancer cells and was shown to achieve plasma concentrations in patients that are effective in vitro without causing significant toxicity.

While S9788 combined with doxorubicin led to a partial response in one patient and was generally safe, it also caused dose-dependent cardiotoxic effects, including increased QT intervals, which raised concerns about potential severe cardiac arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer. Punt, CJ., Voest, EE., Tueni, E., et al.[2019]

The novel doxorubicin (DOX) prodrug forms stable micelles in water, which are about 80 nm in diameter and can carry a high drug loading of approximately 40%, reducing inactive materials and minimizing drug leakage.

In vitro tests show that this prodrug exhibits high anticancer efficacy, suggesting it could be a promising strategy for developing new prodrugs for various anticancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel nanoassembled doxorubicin prodrug with a high drug loading for anticancer drug delivery. [2020]

The study developed a sensitive UPLC-MS/MS method to detect doxorubicin and its prodrug form (DOX-S-S-DOX) in human breast cancer cells, providing insights into their pharmacological mechanisms and antitumor effects.

DOX-S-S-DOX showed greater anticancer activity and reduced toxicity compared to traditional doxorubicin, although it was found to be unstable during storage, highlighting the need for prompt sample preparation to ensure accurate analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A sensitive liquid chromatography/electrospray tandem mass spectroscopy method for simultaneous quantification of a disulfide bond doxorubicin conjugation prodrug and activated doxorubicin: Application to cellular pharmacokinetic and catabolism studies. Zheng, N., Wang, X., Wang, Y., et al.[2017]

Doxorubicin, an anthracycline, has been shown to be effective in adjuvant therapy for metastatic breast cancer, with clinical evidence supporting its safety and efficacy over follow-up periods of up to 19 years.

Trials at the University of Texas M.D. Anderson Cancer Center indicate that doxorubicin can be administered with manageable acute side effects and minimal long-term toxicity, leading to improved disease-free and overall survival rates compared to regimens without doxorubicin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present status of anthracyclines in the adjuvant treatment of breast cancer. Hortobágyi, GN., Buzdar, AU.[2018]

Aldoxorubicin, administered at a maximum tolerated dose of 350 mg/m², was found to be acceptably safe for patients with advanced solid tumors, with no significant cardiac toxicities reported despite some patients experiencing elevated troponin levels.

In terms of efficacy, 20% of patients achieved a partial response, and 40% had stable disease, with improved outcomes observed in patients with advanced soft tissue sarcoma, where 38% had a partial response and median overall survival reached 21.71 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma. Chawla, SP., Chua, VS., Hendifar, AF., et al.[2015]

The synthesized doxorubicin prodrug (prodrug 1) demonstrated safety up to a dose of 24 mg/kg in an Ehrlich Ascites Carcinoma mouse model, indicating a potential for reduced cardiotoxicity compared to traditional doxorubicin.

Prodrug 1 showed improved pharmacokinetics, with 3- to 16-fold lower concentrations in normal tissues compared to doxorubicin, suggesting it may minimize side effects while maintaining efficacy in targeting tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and biodistribution studies of a beta-galactoside prodrug of doxorubicin for improvement of tumor selective chemotherapy. Devalapally, H., Rajan, KS., Akkinepally, RR., et al.[2019]

The study developed six new nanoconjugates using polyhedral oligosilsesquioxanes (POSS) to deliver anthracycline drugs like doxorubicin and daunorubicin, which could help reduce the cardiovascular side effects associated with these chemotherapy agents.

These nanoconjugates demonstrated a controlled drug release profile, with up to 75% of the drug released over 42 hours, suggesting they could allow for lower doses of anthracyclines while maintaining efficacy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Polyhedral Silsesquioxanes [POSS(OH)32] as Anthracycline Nanocarriers-Potential Anticancer Prodrugs. Piorecka, K., Kurjata, J., Stanczyk, WA.[2021]

The novel redox-sensitive hydroxyethyl starch-doxorubicin conjugate (HES-SS-DOX) allows for targeted delivery of doxorubicin (DOX) to tumors, improving its effectiveness while reducing side effects compared to free DOX.

HES-SS-DOX demonstrates a longer plasma half-life and enhanced tumor accumulation, leading to better antitumor efficacy and lower toxicity in vivo, making it a promising candidate for safer cancer chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redox-Sensitive Hydroxyethyl Starch-Doxorubicin Conjugate for Tumor Targeted Drug Delivery. Hu, H., Li, Y., Zhou, Q., et al.[2022]

Diltiazem (DIL) significantly enhances the effectiveness of doxorubicin (DOX) in breast cancer cells by reversing drug resistance, as evidenced by a more than fourfold reduction in ABCB1 gene expression and increased expression of protective genes FOXO3a and p53.

DIL also protects against DOX-induced cardiotoxicity in Wistar rats, demonstrated by improved cardiac enzyme levels and histopathological preservation of cardiac architecture after DOX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of doxorubicin-induced expression of the multidrug resistance gene in breast cancer cells by diltiazem and protection against cardiotoxicity in experimental animals. Al-Malky, HS., Osman, AM., Damanhouri, ZA., et al.[2022]

Prodrugs of doxorubicin were created that only become active in the presence of the specific antibody 93F3, ensuring targeted activation and minimizing side effects.

In laboratory tests, these prodrugs effectively reduced the growth of human cancer cells when activated by 93F3, demonstrating their potential as a targeted cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldolase antibody activation of prodrugs of potent aldehyde-containing cytotoxics for selective chemotherapy. Sinha, SC., Li, LS., Watanabe, S., et al.[2013]

The doxorubicin conjugate, designed to target prostate-specific antigen (PSA), significantly increased tumor exposure to doxorubicin by 2.5 times compared to standard doxorubicin, enhancing its potential efficacy in treating prostate cancer.

Importantly, the prodrug resulted in lower doxorubicin concentrations in heart tissue, which may reduce the risk of dose-limiting toxicity commonly associated with doxorubicin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites. Wong, BK., DeFeo-Jones, D., Jones, RE., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

In Vivo Antitumoral Efficacy of PhAc-ALGP-Doxorubicin, an Enzyme-Activated Doxorubicin Prodrug, in Patient-Derived Soft Tissue Sarcoma Xenograft Models. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A novel nanoassembled doxorubicin prodrug with a high drug loading for anticancer drug delivery. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A sensitive liquid chromatography/electrospray tandem mass spectroscopy method for simultaneous quantification of a disulfide bond doxorubicin conjugation prodrug and activated doxorubicin: Application to cellular pharmacokinetic and catabolism studies. [2017]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Present status of anthracyclines in the adjuvant treatment of breast cancer. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and biodistribution studies of a beta-galactoside prodrug of doxorubicin for improvement of tumor selective chemotherapy. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Polyhedral Silsesquioxanes [POSS(OH)32] as Anthracycline Nanocarriers-Potential Anticancer Prodrugs. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Redox-Sensitive Hydroxyethyl Starch-Doxorubicin Conjugate for Tumor Targeted Drug Delivery. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Modulation of doxorubicin-induced expression of the multidrug resistance gene in breast cancer cells by diltiazem and protection against cardiotoxicity in experimental animals. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Aldolase antibody activation of prodrugs of potent aldehyde-containing cytotoxics for selective chemotherapy. [2013]

13. United States pubmed.ncbi.nlm.nih.gov

PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites. [2013]