SON-1010 + Atezolizumab for Ovarian Cancer

Not currently recruiting at 3 trial locations

Overseen By Richard Kenney, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sonnet BioTherapeutics

Must not be taking: Systemic steroids, Biotin

Disqualifiers: Active infection, Autoimmune disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called SON-1010, both alone and in combination with atezolizumab, for individuals with advanced solid tumors and ovarian cancer unresponsive to platinum-based treatments. The trial aims to evaluate the effectiveness of these treatments together and how the body processes them. Suitable participants include those with ovarian cancer that recurred within six months after their last platinum treatment and who have not succeeded with other therapies. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in participants and measure its effectiveness in an initial, smaller group, offering a chance to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain conditions like recent use of investigational agents, immunotherapy, or high-dose steroids may affect eligibility, so 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 using SON-1010 with atezolizumab is safe for people. Studies involving patients with platinum-resistant ovarian cancer and other solid tumors found that this combination is well-tolerated. Patients could handle a maximum dose of 1200 ng/kg without serious problems.

These studies reported no major side effects, suggesting the treatment is generally safe. The combination also showed potential in helping treat cancer. Overall, the safety data for SON-1010 plus atezolizumab appears positive, making this treatment a viable option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for platinum-resistant ovarian cancer, which often include chemotherapy and bevacizumab, SON-1010 is unique because it is an experimental drug that works by enhancing the immune system's response to cancer. Researchers are excited about SON-1010 because it is designed to be used in combination with atezolizumab, a checkpoint inhibitor that helps unleash the immune system against cancer cells. This combination has the potential to offer a new mechanism of action that might improve outcomes for patients who have limited options with existing therapies. By targeting the immune system more effectively, SON-1010 may provide a promising alternative to current treatment methods.

What evidence suggests that this trial's treatments could be effective for platinum-resistant ovarian cancer?

Research shows that the combination of SON-1010 and atezolizumab, which participants in this trial may receive, may help treat ovarian cancer unresponsive to standard treatments. In earlier studies, one patient experienced a 44% reduction in tumor size. SON-1010 boosts the body's immune system, potentially enhancing the effectiveness of atezolizumab. This combination has demonstrated safety, with a strong safety record in patients. Overall, early results suggest this treatment could benefit ovarian cancer patients who haven't succeeded with other treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Richard T Kenney, MD

Principal Investigator

Sonnet BioTherapeutics

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Platinum-resistant Ovarian Cancer (PROC) who've tried standard treatments without success. They must have an ECOG performance status ≤1, indicating they are fully active or restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. Participants need proper organ and bone marrow function, no severe allergies to study drugs, not pregnant or breastfeeding, willing to use effective birth control, and able to consent.

Inclusion Criteria

Willing and able to provide signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

My organs and bone marrow are working well without any medical help.

I am using effective birth control and will not donate sperm for 90 days after the last study drug dose.

Exclusion Criteria

Pregnancy and/or lactation

I have no unresolved noninfectious illnesses within the last 14 days.

I haven't needed antibiotics or antivirals, including for COVID-19, in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SON-1010 in combination with Atezolizumab to assess safety, tolerability, and PK/PD

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SON-1010

Trial Overview The trial is testing SON-1010 combined with Atezolizumab in patients with advanced solid tumors (Part 1) and specifically those with PROC (Part 2). It's an open-label study meaning everyone knows what treatment they're getting. The goal is to assess safety, how well the body tolerates it, and how the drug moves through and affects the body.

How Is the Trial Designed?

Group I: Randomized Arm #2 in Patients with Platinum-resistant Ovarian Cancer Experimental Treatment 1 Intervention

SON-1010 @ RP2D + Atezolizumab

Group II: Randomized Arm #1 in Patients with Platinum-resistant Ovarian Cancer Experimental Treatment 1 Intervention

SON-1010 @ RP2D Alone

Group III: RP2D Expansion in Patients with Platinum-resistant Ovarian Cancer Experimental Treatment 1 Intervention

RP2D Dose of SON-1010 + Atezolizumab

Group IV: Dose Level 5 Experimental Treatment 1 Intervention

SON-1010 Dose Level 5 + Atezolizumab

Group V: Dose Level 4 Experimental Treatment 1 Intervention

SON-1010 Dose Level 4 + Atezolizumab

Group VI: Dose Level 3 Experimental Treatment 1 Intervention

SON-1010 Dose Level 3 + Atezolizumab

Group VII: Dose Level 2 Experimental Treatment 1 Intervention

SON-1010 Dose Level 2 + Atezolizumab

Group VIII: Dose Level 1 Experimental Treatment 1 Intervention

SON-1010 Dose Level 1 + Atezolizumab

Group IX: Randomized Arm #3 in Patients with Platinum-resistant Ovarian Cancer Active Control 1 Intervention

Standard of Care

Who Is Running the Clinical Trial?

Sonnet BioTherapeutics

Lead Sponsor

Trials

4

Recruited

240+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

A 64-year-old woman with recurrent ovarian cancer, previously unresponsive to standard therapies, showed a near-complete response to the immunotherapy atezolizumab after three cycles, indicating potential efficacy in this patient population.

The patient's tumor exhibited loss of MLH1 and PMS2 proteins, suggesting that identifying specific biomarkers may be crucial for selecting effective treatments for ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dramatic response to single-agent atezolizumab in a patient with MSI-H serous ovarian cancer. Ak, N., Vatansever, S.[2022]

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

In a study of 44 women with recurrent ovarian cancer treated with immune checkpoint inhibitors, the overall response rate was 14.2%, with a notable correlation between platinum sensitivity and response in high-grade serous ovarian cancer (HGSOC) patients.

Severe immune-related adverse events (irAEs) occurred in 47.7% of patients, with elevated hepatic or pancreatic enzymes being the most common, and a higher number of gene mutations appeared to protect against these specific adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. Hinchcliff, E., Hong, D., Le, H., et al.[2023]

The phase I clinical trial involving 19 ovarian cancer patients demonstrated that a vaccine using Th17-inducing dendritic cells is safe, with no severe adverse events reported, and successfully induces immune responses against the folate receptor alpha (FRα).

Of the 18 patients evaluated for efficacy, 39% remained recurrence-free after a median follow-up of 49.2 months, suggesting that the vaccine may contribute to prolonged remission in ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients. Block, MS., Dietz, AB., Gustafson, MP., et al.[2020]

In a phase Ib study involving 20 patients with platinum-resistant ovarian cancer, the combination of atezolizumab and bevacizumab demonstrated a safety profile consistent with the individual drugs, with 95% experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment resulted in a 15% overall response rate, with some patients achieving durable responses lasting up to 18.9 months, and a disease control rate of 55%, indicating potential efficacy in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. Moroney, JW., Powderly, J., Lieu, CH., et al.[2021]

In a phase III trial involving newly diagnosed stage III/IV ovarian cancer patients, the addition of atezolizumab to standard therapy did not significantly improve overall survival compared to placebo, with a hazard ratio of 0.92 in the intent-to-treat population.

Patient-reported outcomes related to symptoms, functioning, and quality of life showed no significant differences between the atezolizumab and placebo groups, indicating that the treatment did not impose additional burdens on patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer. Pignata, S., Bookman, M., Sehouli, J., et al.[2023]

Atezolizumab, a PD-L1 inhibitor, was well tolerated in patients with advanced ovarian and uterine cancers, with no new safety concerns and mostly mild treatment-related adverse events.

Preliminary results showed anti-tumor activity in some patients, with long durations of response, suggesting that atezolizumab may be a promising treatment option for these cancers, especially in those with high microsatellite instability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. Liu, JF., Gordon, M., Veneris, J., et al.[2019]

Citations

1. onclive.com onclive.com/view/son-1010-plus-atezolizumab-is-safe-displays-preliminary-efficacy-in-platinum-resistant-ovarian-cancer

SON-1010 Plus Atezolizumab Is Safe, Displays ... - OncLive Regarding efficacy, 1 patient with platinum-resistant ovarian cancer experienced a partial response with a 44% reduction in tumor size and 2- ...

2. sonnetbio.com sonnetbio.com/news-media/press-releases/detail/124/sonnets-son-1010-demonstrates-a-strong-safety-profile-in

Sonnet's SON-1010 Demonstrates a Strong Safety Profile ... The maximum tolerated dose (MTD) of SON-1010 was set at 1200 ng/kg in combination with atezolizumab in patients with platinum-resistant ovarian cancer (PROC).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05756907

NCT05756907 | Combination of SON-1010 (IL12-FHAB) ... This is a Phase 1b/2a, open-label, adaptive-design outpatient study to assess the safety, tolerability, and PK/PD of SON-1010 in combination with ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1048891X24163633

TP013/#1585 Sb221: a proof-of-concept study to assess ... We hypothesize that SON-1010 may 'warm up' the TME to improve checkpoint inhibitor effectiveness in immunologically-active tumors like PROC that have high ...

5. firstwordpharma.com firstwordpharma.com/story/5986208

Sonnet BioTherapeutics Expands Clinical Evaluation of ... Sonnet's lead product, SON-1010 (IL12-FHAB), is being evaluated in combination with atezolizumab (Tecentriq®) in patients with advanced ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5629

SB221: A proof-of-concept study to assess the combination ... SB221 is a Phase 1b/2a multicenter, dose-escalation and proof-of-concept study to assess the safety, tolerability, PK, PD, and efficacy of SON-1010 ...

7. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/sonnet-releases-positive-safety-data-for-son-1010-in-phase-1b-2a/

Sonnet Releases Positive Safety Data for SON-1010 in ... Sonnet BioTherapeutics announced positive safety data for SON-1010 (IL12-FHAB) at the highest dose combined with atezolizumab in a Phase ...