Lurbinectedin + Immunotherapy for Soft Tissue Sarcoma

(LINNOVATE Trial)

Overseen By Victoria Chua-Alcala, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ERLINDA M GORDON

Must not be taking: Corticosteroids, Chemotherapy, Immunotherapy, others

Disqualifiers: CNS metastases, Autoimmune disease, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open label, dose-seeking phase 1/2 study using escalating doses of LURBINECTEDIN administered intravenously with fixed doses of IPILIMUMAB and NIVOLUMAB administered intravenously.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had anticancer treatment within 2-3 weeks before starting the trial, and you should not be on certain immunotherapies or systemic immunosuppressants.

What makes the drug Lurbinectedin unique for treating soft tissue sarcoma?

Lurbinectedin is unique because it combines with immunotherapy to potentially enhance the body's immune response against soft tissue sarcoma, offering a novel approach compared to traditional chemotherapy or radiation treatments. ^{1 2 3 4 5}

Research Team

Erlinda M Gordon, MD

Principal Investigator

Sarcoma Oncology Research Center

Eligibility Criteria

Adults over 18 with advanced soft tissue sarcoma, either previously treated (for Phase 1) or untreated (for Phase 2), can join this trial. They must have measurable disease, good blood counts and organ function, understand the study risks, consent in writing, be willing to follow procedures for the study's duration, use effective contraception, and have a life expectancy of at least 3 months. Those with certain health conditions or treatments are excluded.

Inclusion Criteria

All women of childbearing potential must have a negative pregnancy test and all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose

I am 18 years old or older.

Life expectancy of at least 3 months

Exclusion Criteria

I haven't had vaccines for infectious diseases in the last 4 weeks.

Current, active, or previous history of heavy alcohol abuse

I am on immunosuppressive therapy or I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Phase 1

Participants receive escalating doses of LURBINECTEDIN with fixed doses of IPILIMUMAB and NIVOLUMAB to determine the maximum tolerated dose (MTD).

6 weeks

Visits every 3 weeks for dose administration

Phase 2

Participants receive LURBINECTEDIN at the MTD and fixed doses of IPILIMUMAB and NIVOLUMAB to assess overall safety and potential efficacy.

12 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Lurbinectedin

Trial Overview The LINNOVATE trial is testing different doses of Lurbinectedin given through IV along with set doses of Ipilimumab and Nivolumab also administered via IV. It's an open-label phase 1/2 study which means everyone knows what treatment they're getting and there are two parts: dose-finding followed by effectiveness testing.

Participant Groups

Group I: Phase 1/2 study using lurbinectedin, ipilimumab and nivolumab for advanced soft tissue sarcoma Experimental Treatment 1 Intervention

This is an open label, dose-seeking phase 1/2 study using escalating doses of LURBINECTEDIN administered intravenously with fixed doses of IPILIMUMAB and NIVOLUMAB administered intravenously. I. Dose Escalation Phase 1 of Study: The study will employ the standard "cohort of three" design (Storer, 1989). II.Phase 2 of Study: Following completion of dose escalation, an additional 28-34 previously untreated participants will receive LURBINECTEDIN at the MTD and fixed doses of IPILIMUMAB and NIVOLUMAB to assess overall safety and potential efficacy in a larger number of participants.

Lurbinectedin is already approved in United States, European Union for the following indications:

Approved in United States as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Approved in European Union as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Who Is Running the Clinical Trial?

ERLINDA M GORDON

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, and while there are various treatment options for early-stage disease, advanced-stage MF still lacks effective therapies, highlighting a significant unmet medical need.

Current research is focused on novel agents like brentuximab vedotin and mogamulizumab in randomized phase 3 trials, which may lead to more effective targeted therapies for advanced MF and Sézary syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat mycosis fungoides and Sézary syndrome. Whittaker, S., Hoppe, R., Prince, HM.[2021]

In a phase II pilot study involving 24 patients with chronic lymphocytic leukemia (CLL) who had previously undergone chemotherapy, alemtuzumab demonstrated significant efficacy, with 33% of patients achieving a major response and a median survival time of 35.8 months.

Despite its effectiveness, the treatment was associated with a high incidence of opportunistic infections due to low lymphocyte counts, suggesting that future studies should implement mandatory antimicrobial prophylaxis to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. Rai, KR., Freter, CE., Mercier, RJ., et al.[2017]

Alemtuzumab is highly effective for treating refractory Sézary syndrome (SS), showing an overall response rate of 81% and a complete response rate of 38% in a meta-analysis of 308 patients, compared to lower response rates in mycosis fungoides (MF).

Patients receiving alemtuzumab experienced more side effects, particularly with intravenous administration and higher doses, but low-dose subcutaneous administration resulted in fewer adverse events, making it a safer option for SS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab is an effective third-line treatment versus single-agent gemcitabine or pralatrexate for refractory Sézary syndrome: a systematic review. Stewart, JR., Desai, N., Rizvi, S., et al.[2022]

In a phase II study involving 8 patients with advanced cutaneous T-cell lymphoma, alemtuzumab showed a modest overall response rate of 38%, with some patients achieving partial remission, but responses were short-lived, lasting less than 3 months.

The treatment was associated with significant toxicity, including severe cytopenias and infectious complications, indicating that while alemtuzumab has some biological activity, its safety profile and limited efficacy suggest the need for further research into combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab. Kennedy, GA., Seymour, JF., Wolf, M., et al.[2021]

In a study of 44 mycosis fungoides patients treated with chlormethine/mechlorethamine, those on maintenance therapy achieved a 65.22% progression-free survival rate, with a median time to progression of 29.45 months.

Both active and maintenance treatments with chlormethine/mechlorethamine led to significant improvements in skin condition (measured by mSWAT) and quality of life, suggesting its efficacy as a maintenance therapy for patients in remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to Chlormethine/Mechlorethamine gel Maintenance Treatment Regimen in Patients With Mycosis Fungoides: A Single-center Retrospective Study. Correia, E., Krishnasamy, S., Suriano, JG., et al.[2022]

References

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

How I treat mycosis fungoides and Sézary syndrome. [2021]

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

Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. [2017]

3. France pubmed.ncbi.nlm.nih.gov

Alemtuzumab is an effective third-line treatment versus single-agent gemcitabine or pralatrexate for refractory Sézary syndrome: a systematic review. [2022]

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

Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab. [2021]

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

Response to Chlormethine/Mechlorethamine gel Maintenance Treatment Regimen in Patients With Mycosis Fungoides: A Single-center Retrospective Study. [2022]