Atezolizumab +/− Selinexor for Sarcoma

Recruiting at 9 trial locations

Overseen by Alice P Chen

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Pregnancy, CNS metastases, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing if atezolizumab alone or with selinexor can shrink tumors in patients with a rare type of cancer called alveolar soft part sarcoma. Atezolizumab boosts the immune system to fight cancer, and selinexor stops cancer cells from growing. The goal is to see if these treatments work better than the usual care.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have had chemotherapy or radiotherapy within 4 weeks before the study, and you should not be on systemic immunosuppressive medications within 2 weeks prior to starting. If you're on other cancer treatments, you need to stop them at least 4 weeks before the trial begins.

Is the combination of Atezolizumab and Selinexor safe for humans?

Atezolizumab has been studied for safety in various cancers, including lung cancer, and is generally considered safe, though it can cause mild skin rashes and, in rare cases, severe skin reactions. Selinexor's safety profile is not detailed in the provided research, but Atezolizumab alone has been used safely in many patients. ^{1 2 3 4 5}

What makes the drug Atezolizumab +/− Selinexor unique for treating sarcoma?

Atezolizumab is a unique drug for sarcoma because it is a PD-L1 blocking antibody that enhances the body's immune response against cancer cells, and it has been approved for treating alveolar soft part sarcoma, a rare type of sarcoma. Combining it with Selinexor, which inhibits nuclear export of tumor suppressor proteins, may offer a novel approach by targeting cancer cells in two different ways. ^{1 2 3 5 6}

Research Team

Alice P Chen

Principal Investigator

National Cancer Institute LAO

Eligibility Criteria

Adults (18+) with alveolar soft part sarcoma, a rare cancer, who can't be cured by surgery. They should have measurable tumor growth and acceptable organ function. HIV-positive patients must have an undetectable viral load on therapy. Participants need to agree to use contraception if applicable and provide biopsy samples for research.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

Absolute neutrophil count >= 1,500/mcL

Platelets >= 100,000/mcL

Exclusion Criteria

History of severe allergic, anaphylactic, or other hypersensitivity reactions to specific compounds

I had mild or moderate infection symptoms within the last 2 weeks.

I have had treatment for any painful cancer spots before joining.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial phase to assess the safety of selinexor in combination with atezolizumab

4 weeks

Treatment

Patients receive atezolizumab and selinexor or atezolizumab alone in 28-day cycles

Up to 2 years

Visits every 28 days for treatment and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• Selinexor (Selective Inhibitors of Nuclear Export (SINE))

Trial Overview The trial is testing the effectiveness of Atezolizumab alone or combined with Selinexor against standard treatments for shrinking tumors in alveolar soft part sarcoma. It explores how these drugs might help the immune system fight cancer or block proteins that aid in cancer cell growth.

Participant Groups

Group I: Arm II (atezolizumab) Experimental Treatment 6 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Patients also undergo ECHO at baseline, biopsy at baseline and cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study.

Group II: Arm I (atezolizumab, selinexor) Experimental Treatment 7 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 8 of cycle 1, and then on day 1 of subsequent cycles. Patients also receive selinexor PO QW on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO at baseline, biopsy at baseline, cycle 1 day 8 and cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

In a real-world study of 1002 patients with previously treated non-small cell lung cancer (NSCLC), atezolizumab showed an 18-month overall survival rate of 41.1%, confirming its effectiveness outside of clinical trial settings.

The safety profile was acceptable, with an overall adverse event rate of 43.9% and immune-related adverse events at 19.0%, but caution is advised for patients with poorer performance status (ECOG ≥ 2), as they had a significantly lower survival rate of 14.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL). Miura, S., Nishio, M., Akamatsu, H., et al.[2023]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

References

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

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma. [2020]

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

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL). [2023]

5. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. [2023]