SQ3370 for Cancer

No longer recruiting at 12 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SQ3370, a combination of a doxorubicin prodrug and SQL 70 - Shasqi, for individuals with advanced solid tumors, such as certain sarcomas or head and neck cancers. The trial aims to assess the safety of SQ3370 and its effectiveness in shrinking tumors. Participants will receive a biopolymer injection directly into the tumor and a series of IV doses of the study drug. This trial suits those with relapsed or hard-to-treat cancers who have not found success with other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

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

Research has shown that SQ3370 has been tested in people with advanced solid tumors. In these studies, the treatment involved injecting a special substance directly into the tumor, followed by administering a series of drug doses through an IV. Early results suggest that this method is safe and well-tolerated by participants.

Some patients experienced side effects, which is common with cancer treatments. However, these side effects were generally manageable and did not require stopping the treatment. The treatment targets the tumor directly while delivering drugs throughout the body, aiming to protect healthy tissues. This approach allows researchers to monitor and adjust doses carefully to ensure safety.

Overall, while more information is needed, early studies provide a promising view of SQ3370's safety for patients with advanced cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SQ3370 because it offers a novel approach to treating cancers like squamous-cell carcinoma of the head and neck and soft tissue sarcomas. Unlike traditional chemotherapy, which often affects the whole body, SQ3370 targets tumors directly with an innovative two-step process. First, the SQL70 biopolymer is injected into the tumor, localizing treatment. Then, the SQP33 protodrug is activated, potentially minimizing side effects by focusing on cancerous cells. This method could lead to more effective and less toxic cancer treatments, setting it apart from existing therapies.

What evidence suggests that SQ3370 could be an effective treatment for advanced solid tumors?

Research has shown that SQ3370, a treatment combining a special protein and a modified drug, holds promise for advanced solid tumors. In this trial, participants will receive varying doses of SQ3370, with some in the dose escalation cohorts receiving higher doses. One study involved 14 patients with soft tissue sarcoma receiving this treatment, and two of them (14.3%) experienced tumor shrinkage. Additionally, high doses of SQ3370 have affected the immune system, potentially aiding in the treatment of both localized and widespread cancer. These early results are encouraging and suggest that SQ3370 could be effective for difficult-to-treat cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

Jim Williams, MD

Principal Investigator

Shasqi, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: P2a Group 2 (10 mL SQL70 and 500 mg/m^2/ of SQP33 for 2 days and and 250 mg/m^2/ of SQP33 for 1 day) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 500 mg/m\^2 of SQP33 infused on Day 1 and 2 with 250 mg/m\^2 of SQP33 infused on each Day 3 in subjects with locally advanced, unresectable or metastatic soft tissue sarcomas who are anthracycline naïve

Group II: P2a Group 2 (10 mL SQL70 and 250 mg/m^2/day of SQP33 for five days) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day with 250 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced, unresectable or metastatic soft tissue sarcomas who are anthracycline naïve

Group III: P2a Group 1 (Extremity STS) (20 mL SQL70 and 250 mg/m^2/Day of SQP33) Experimental Treatment 1 Intervention

20 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 250 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with soft tissue sarcomas of the extremity

Group IV: Dose Escalation Cohort 9 (10 mL SQL70 and 315 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 315 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group V: Dose Escalation Cohort 8 (10 mL SQL70 and 250 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 250 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group VI: Dose Escalation Cohort 7 (10 mL SQL70 and 185 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 185 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group VII: Dose Escalation Cohort 6 (10 mL SQL70 and 125 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 125 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group VIII: Dose Escalation Cohort 5 (10 mL SQL70 and 85 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 85 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group IX: Dose Escalation Cohort 4 (10 mL SQL70 and 58 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 58 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors.

Group X: Dose Escalation Cohort 3 (10 mL SQL70 and 32 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 32 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors.

Group XI: Dose Escalation Cohort 2 (10 mL SQL70 and 16 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 16 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors.

Group XII: Dose Escalation Cohort 1 (10 mL SQL70 and 8 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 8 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group XIII: Dose Escalation Cohort (20 mL SQL70 and 85 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

20 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 85 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group XIV: Dose Escalation Cohort (20 mL SQL70 and 125 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

20 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 125 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Group XV: Cohort A (10 mL SQL70 and 185 mg/m^2 of SQP33) Experimental Treatment 1 Intervention

10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 185 mg/m\^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors

Who Is Running the Clinical Trial?

Shasqi, Inc.

Lead Sponsor

Trials

1

Recruited

150+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04106492

NCT04106492 | Phase 1/2a Study of SQ3370 in Patients ... Phase 1: Inclusion Criteria: Diagnosis of advanced soft tissue sarcoma or other solid tumors; Adequate hematologic, hepatic, renal, and coagulation function ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40502603/

A first-in-human, Phase 1/2a, open-label study of SQ3370 ... Phase 2a enrolled 14 soft tissue sarcoma patients at 12x Dox. There was an unconfirmed objective response rate (ORR) of 14.3% (2/14 patients) ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.06.02.25328445v1.full.pdf

A first-in-human, Phase 1/2a, open-label study of SQ3370, ... The efficacy analysis set included all patients who received at least 1 dose of SQL70 biopolymer and 1 dose of SQP33 protodrug and had at least ...

4. medrxiv.org medrxiv.org/content/10.1101/2025.06.02.25328445v1.full-text

A first-in-human, Phase 1/2a, open-label study of SQ3370, ... The efficacy analysis set included all patients who received at least 1 dose of SQL70 biopolymer and 1 dose of SQP33 protodrug and had at least ...

5. shasqi.com shasqi.com/post/shasqi-advances-sq3370-to-phase-2-in-solid-tumors

Shasqi Advances SQ3370 to Phase 2 in Solid Tumors High dose levels of SQ3370 show novel immune-regulatory effects that could treat both local and metastatic lesions. SAN FRANCISCO, September 12, ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT308745

Effect of local activation via SQ3370 on the safety ... Methods: SQL70 is injected at the tumor site followed by SQP33 given systemically. The prodrug is captured by the biomaterial due to their complementary ...

7. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/p/NCT04106492.html

Phase 1/2a Study of SQ3370 in Patients With Advanced Solid ... Phase 1: Inclusion Criteria: 1. Diagnosis of advanced soft tissue sarcoma or other solid tumors 2. Adequate hematologic, hepatic, renal, and coagulation ...