STI-6643 for Advanced Cancers

Not currently recruiting at 3 trial locations

Overseen By Mike Royal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sorrento Therapeutics, Inc.

Must not be taking: Anti-CD47, SIRPα antibodies

Disqualifiers: CNS involvement, Active infection, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, STI-6643, for individuals with advanced solid tumors that have recurred or are unresponsive to standard treatments. The goal is to determine a safe dose and evaluate the treatment's effectiveness. Participants will receive the treatment through an IV, with the first four doses administered weekly, followed by doses every two weeks. This trial may suit those with confirmed advanced solid tumors who have not succeeded with other treatments and have a life expectancy of more than 12 weeks. 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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, there are specific time requirements for stopping certain treatments before starting the trial, such as systemic anti-tumor treatments, irradiation, and immunosuppressive therapy. It's best to discuss your current medications with the trial team to see if they affect your eligibility.

Is there any evidence suggesting that STI-6643 is likely to be safe for humans?

Research has shown that STI-6643 was safe in earlier studies. In tests with animals like monkeys, STI-6643 was well-tolerated even at high doses, with no major harmful effects on red blood cells or certain white blood cells. This suggests the treatment might be safe for humans as well. However, this study marks the first time STI-6643 is being tested in humans. While animal studies appear promising, human trials are necessary to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced cancers, which often include chemotherapy, radiation, and targeted therapies, STI-6643 is unique because it is administered intravenously in a concentrated form, aiming to deliver a potent dose directly to the cancer cells. Researchers are excited about STI-6643 because it offers a novel delivery method that could potentially enhance the effectiveness of cancer treatment by ensuring that higher concentrations of the drug reach the tumor site. This targeted approach could lead to improved outcomes with potentially fewer side effects compared to traditional therapies.

What evidence suggests that STI-6643 might be an effective treatment for advanced cancers?

Research has shown that STI-6643, the treatment under study in this trial, could be a promising option for advanced cancers. Studies have found that it can shrink or slow the growth of cancer cells. This treatment targets a protein called CD47 on cancer cells, which typically helps them evade the immune system. By blocking CD47, STI-6643 enables the immune system to find and attack cancer cells more effectively. Early tests also suggest it is well-tolerated, with minimal impact on blood cell counts. These findings make STI-6643 a strong candidate for further research as a cancer treatment. ^{2 6 7 8 9}

Who Is on the Research Team?

Mike Royal, MD

Principal Investigator

Sorrento Therapeutics, Inc.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that have relapsed or are unresponsive to standard treatments can join this trial. They must have a life expectancy over 12 weeks, acceptable blood counts and organ function, and no recent other treatments or surgeries. Women of childbearing potential need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

I am a woman who can have children and have a negative pregnancy test.

I am a woman who is either postmenopausal, cannot have children, or will use birth control during and after the study.

I am a man who is either surgically sterile or will use contraception during and 30 days after the study.

Exclusion Criteria

I have not had an infection needing treatment in the last 3 days.

I do not have serious heart issues or uncontrolled high blood pressure.

I have an infection with HTLV1, HBV, or HCV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Participants receive STI-6643 intravenously with dose escalation to determine MTD and RP2D using a 3+3 study design

4 weeks

Weekly visits for 4 weeks

Therapeutic Dose Escalation

Participants continue receiving STI-6643 biweekly for Cycles 2 and up

Up to 31 months

Biweekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• STI-6643

Trial Overview The trial is testing STI-6643, an experimental drug given by IV for those with certain advanced cancers. It's the first time humans will receive it (phase 1), focusing on finding a safe dose while observing its effectiveness against tumors.

How Is the Trial Designed?

Group I: STI-6643 Experimental Treatment 1 Intervention

STI-6643 will be provided in a single use 10-mL high borosilicate type 1 glass vial at a concentration of 500mg/10 mL (50 mg/mL) administered intravenously weekly for 4 weeks, then biweekly for Cycles 2 and up.

Who Is Running the Clinical Trial?

Sorrento Therapeutics, Inc.

Lead Sponsor

Trials

48

Recruited

2,000+

Published Research Related to This Trial

The maximum tolerated dose (MTD) of OSI-461 was determined to be 1,000 mg taken orally twice daily in combination with mitoxantrone, with the combination generally well tolerated by patients with advanced solid tumors.

Out of the patients studied, 10% experienced a partial response and 50% had stable disease, indicating that while the combination was safe, the response rates were similar to those seen with mitoxantrone alone, leading to the decision not to pursue further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone. Resta, LP., Pili, R., Eisenberger, MA., et al.[2021]

In a study of 20 patients with advanced gastrointestinal stromal tumors (GISTs), ecteinascidin 743 (ET-743) showed limited efficacy, with no objective responses and only two patients experiencing disease stabilization for 4 and 10 months.

The treatment was generally well-tolerated, with severe toxicities being reversible and primarily consisting of grade 3 transaminitis in 10 patients, indicating a safety profile but highlighting the primary resistance of GISTs to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors. Ryan, DP., Puchalski, T., Supko, JG., et al.[2019]

APR-246 effectively reactivates mutant p53 protein in high-grade serous ovarian cancer, showing strong synergy with cisplatin and other chemotherapy agents in primary cancer cells from patients, particularly those with TP53 mutations.

The combination of APR-246 with cisplatin significantly reduced the drug's effective concentration needed to kill cancer cells, indicating that this treatment could enhance the efficacy of chemotherapy in patients with TP53 mutant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancer. Fransson, Å., Glaessgen, D., Alfredsson, J., et al.[2021]

In a phase I study involving 43 patients with advanced solid tumors, MEDI-573 demonstrated a favorable safety profile with no dose-limiting toxicities and only one case of treatment-related hyperglycemia.

While MEDI-573 did not lead to any partial or complete responses in the tumors, 13 out of 39 evaluable patients showed stable disease, indicating some preliminary antitumor activity in a heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Haluska, P., Menefee, M., Plimack, ER., et al.[2021]

In a phase Ib/II clinical trial of APR-246 combined with chemotherapy for metastatic esophageal cancer, TP53 mutation status was found to be an unreliable predictor of response to the treatment, suggesting that other factors should be considered for patient selection.

The study identified SLC7A11 expression as a superior biomarker for predicting sensitivity to APR-246, indicating that it should be used to better stratify patients in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SLC7A11 Is a Superior Determinant of APR-246 (Eprenetapopt) Response than TP53 Mutation Status. Fujihara, KM., Corrales Benitez, M., Cabalag, CS., et al.[2022]

The combination of the ATR inhibitor M6620 and the TOP1 inhibitor topotecan was well tolerated in a phase I study involving 21 patients, allowing for dose escalation to the maximum planned dose, despite some instances of dose-limiting toxicities like thrombocytopenia.

This treatment showed promising efficacy, particularly in patients with platinum-refractory small-cell lung cancer, with two partial responses and several cases of stable disease lasting over three months, indicating potential for further investigation in phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors. Thomas, A., Redon, CE., Sciuto, L., et al.[2022]

The maximum tolerated dose of KOS-862, an epothilone for treating advanced solid tumors or lymphoma, was established at 100 mg/m², with manageable toxicity observed in a study involving 32 patients.

KOS-862 demonstrated a favorable pharmacokinetic profile and showed signs of clinical activity, including tumor shrinkage and stable disease in several patients, indicating its potential effectiveness in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma. Konner, J., Grisham, RN., Park, J., et al.[2021]

In a phase II trial involving 65 patients aged 60 and older with acute myeloid leukemia or myelodysplastic syndrome, the combination of vosaroxin and decitabine showed a high overall response rate of 74%, with 48% achieving complete remission.

Reducing the vosaroxin dose to 70 mg/m2 significantly decreased the incidence of severe mucositis and improved median overall survival to 14.6 months, compared to 5.5 months with the higher dose, indicating a better safety profile while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Daver, N., Kantarjian, H., Garcia-Manero, G., et al.[2019]

Panobinostat, a histone deacetylase inhibitor, shows significant synergy with gemcitabine and paclitaxel, and particularly strong synergistic effects when combined with doxorubicin and carboplatin in treating metastatic ovarian cancer cell lines.

The study utilized in vitro assays on three ovarian cancer cell lines (SK-OV3, CaOV-3, and ES-2) to identify effective drug combinations, suggesting that these combinations could enhance treatment efficacy and warrant further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. Budman, DR., Tai, J., Calabro, A., et al.[2021]

In a phase I trial involving 33 patients with advanced solid tumors, OSI-461 was found to be well-tolerated at a recommended dose of 800 mg taken twice daily with food, which significantly increased its bioavailability.

The study identified dose-limiting toxicities such as grade 3 abdominal pain and fatigue at higher doses, but overall, the drug showed promising pharmacodynamic effects, including increased levels of pGSK-3beta, indicating its potential effectiveness in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose-ranging study of the pharmacokinetics and pharmacodynamics of the selective apoptotic antineoplastic drug (SAAND), OSI-461, in patients with advanced cancer, in the fasted and fed state. O'Bryant, CL., Lieu, CH., Leong, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9161735/

A Novel Affinity Engineered Anti-CD47 Antibody With ... Our data demonstrated STI-6643 was well-tolerated with minimal impact on RBCs and lymphocytes counts (including T cells) at doses up to 300 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35664753/

A Novel Affinity Engineered Anti-CD47 Antibody With ... These data suggest that STI-6643 possesses the characteristics of an effective therapeutic candidate given its potent anti-tumor activity ...

3. researchgate.net researchgate.net/figure/Dose-titration-of-anti-tumor-activity-of-STI-6643-in-the-hematologic-RAJI-xenograft_fig4_360732676

Dose titration of anti-tumor activity of STI-6643 in the hematologic... ... cancer cells. However, current anti-CD47 mAbs have limitations, including off-tumor toxicity and reduced effectiveness in advanced cancers. Additionally ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1378647/full

Targeting the CD47/SIRPα pathway in malignancies Monotherapy involving the blockade of the CD47-SIRPα axis has shown promising outcomes in ovarian cancer, with the combination of pro-phagocytic CD47-SIRPα axis ...

5. biospace.com biospace.com/sorrento-receives-fda-clearance-to-start-clinical-trial-of-anti-cd47-antibody-discovered-from-fully-human-g-mab-library-for-treatment-of-multiple-malignancies

Sorrento Receives FDA Clearance to Start Clinical Trial of ... In preclinical evaluations, STI-6643 displayed decreased red blood cell binding and hemolysis, while maintaining potent anti-tumor activity in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04900519

Study of the Safety and Efficacy of STI-6643 in Subjects ... This is a first-in-human, phase 1, open-label, dose-escalation study of STI-6643 administered by intravenous infusion in subjects with a relapsed/refractory ...

7. researchgate.net researchgate.net/figure/STI-6643-treatment-shows-comparable-anti-tumor-activity-to-reference-clone-Hu5F9-in-the_fig4_360732676

STI-6643 treatment shows comparable anti-tumor activity to ... STI-6643 demonstrates high safety profile in non-human primate... STI-6643 ... tumor toxicity and reduced effectiveness in advanced cancers.

8. medchemexpress.com medchemexpress.com/sti-6643.html?locale=ko-KR&srsltid=AfmBOooRwrkthTDFBR5mlhC_Ic4xTfTjhp7v91oWHnrQI59ud3urZ0Yu

STI-6643 | CD47 Antibody STI-6643 is a fully human IgG4 antibody that targets CD47. STI-6643 displays potent anti-tumor activity with negligible RBC and lymphocyte toxicities.

9. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.884196/full

A Novel Affinity Engineered Anti-CD47 Antibody With ... These data suggest that STI-6643 possesses the characteristics of an effective therapeutic candidate given its potent anti-tumor activity and ...