LINNOVATE: Lurbinectedin, Ipilimumab and Nivolumab for Soft Tissue Sarcoma

NCT05876715 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SOC-2310
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Soft-tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  The maximum tolerated dose (MTD) is defined as the highest safely tolerated dose of lurbinectedin, where not more than one participant experienced a dose limiting toxicity (DLT), with the next higher dose level having at least two participants who experienced DLT.

  6 months

Secondary Outcomes (4)

• Objective response rate

  24 months

• Progression free survival at 6 months

  12 months

• Overall survival

  36 months

• Correlation of response with circulating tumor DNA

  36 months

Study Arms (1)

Phase 1/2 study using lurbinectedin, ipilimumab and nivolumab for advanced soft tissue sarcoma

EXPERIMENTAL

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.

Drug: Lurbinectedin

Interventions

Lurbinectedin DRUG

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.

Also known as: Ipilimumab, Nivolumab

Phase 1/2 study using lurbinectedin, ipilimumab and nivolumab for advanced soft tissue sarcoma

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female ≥ 18 years of age
• Pathologically confirmed diagnosis of locally advanced unresectable or metastatic soft tissue sarcoma
• For the Phase 1 Part of Study, only previously treated participants will be enrolled. For the Phase 2 Part of Study, previously untreated participants will be enrolled.
• Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the principal investigator's IRB/Ethics Committee
• Willingness to comply with all study procedures and availability for the duration of the study.
• Measurable disease by RECIST v1.1
• ECOG performance status ≤ 1
• Life expectancy of at least 3 months
• Acceptable liver function: Bilirubin \< 1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level \< 3.0 ULN);
• AST (SGOT), ALT (SGPT) and alkaline phosphatase \< 3 x ULN (\< 5 x ULN if liver metastases)
• Acceptable renal function: Creatinine \< 1.5 times ULN or \> 60 mL/min (using the Cockcroft Gault formula)
• Acceptable hematologic status (without hematologic support e.g. growth factors or transfusion within 21 days of first dose of study agents): ANC \>= 1500 cells/μL; Platelet count \>= 100,000/μL; Hemoglobin \>= 9.0 g/dL; Normal PT, PTT, INR
• 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.

You may not qualify if:

• Subjects with untreated CNS metastases. Subjects are eligible if CNS metastases have been adequately treated and have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to treatment initiation. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of \<10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment initiation.
• Subjects with carcinomatous meningitis
• Anticancer treatment with radiation therapy, targeted therapy or other antitumor treatment within 2 weeks prior to study entry. Anticancer treatment with chemotherapy within 21 days prior to study entry.
• Subjects who participated in an investigational drug or device study within 14 days prior to study entry
• Females who are pregnant or breast-feeding
• Unwillingness or inability to comply with the study protocol for any reason
• Concurrent or prior immunotherapy with anti-CTLA4 or anti-PD-1 inhibitors
• Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment
• Autoimmune disease including rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis and motor neuropathy considered to be of autoimmune origin (e.g. Guillain-Barre Syndrome)
• Systemic immunosuppression, including HIV positive status with or without AIDS
• Skin rash (psoriasis, eczema) affecting \> 25% body surface area
• Inflammatory bowel disease (Crohn's or ulcerative colitis)
• Ongoing or uncontrolled diarrhea within 4 weeks of trial enrollment
• Recent history of acute diverticulitis, intraabdominal abscess or gastrointestinal obstruction within 6 months of trial enrollment, which are known risk factors for bowel perforation
• Participants with congestive heart failure or recent cardiac event

Sponsors & Collaborators

• ERLINDA M GORDON: lead

Study Sites (1)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

RECRUITING

Related Publications (4)

• Gordon EM, Chawla SP, Tellez WA, Younesi E, Thomas S, Chua-Alcala VS, Chomoyan H, Valencia C, Brigham DA, Moradkhani A, Quon D, Srikureja A, Wong SG, Tseng W, Federman N. SAINT: A Phase I/Expanded Phase II Study Using Safe Amounts of Ipilimumab, Nivolumab and Trabectedin as First-Line Treatment of Advanced Soft Tissue Sarcoma. Cancers (Basel). 2023 Jan 31;15(3):906. doi: 10.3390/cancers15030906.

  PMID: 36765863 BACKGROUND

• Gordon EM, Sankhala KK, Chawla N, Chawla SP. Trabectedin for Soft Tissue Sarcoma: Current Status and Future Perspectives. Adv Ther. 2016 Jul;33(7):1055-71. doi: 10.1007/s12325-016-0344-3. Epub 2016 May 27.

  PMID: 27234989 BACKGROUND

• Belgiovine C, Bello E, Liguori M, Craparotta I, Mannarino L, Paracchini L, Beltrame L, Marchini S, Galmarini CM, Mantovani A, Frapolli R, Allavena P, D'Incalci M. Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models. Br J Cancer. 2017 Aug 22;117(5):628-638. doi: 10.1038/bjc.2017.205. Epub 2017 Jul 6.

  PMID: 28683469 BACKGROUND

• Cespedes MV, Guillen MJ, Lopez-Casas PP, Sarno F, Gallardo A, Alamo P, Cuevas C, Hidalgo M, Galmarini CM, Allavena P, Aviles P, Mangues R. Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models. Dis Model Mech. 2016 Dec 1;9(12):1461-1471. doi: 10.1242/dmm.026369. Epub 2016 Oct 20.

  PMID: 27780828 BACKGROUND

MeSH Terms

Interventions

PM 01183; Ipilimumab; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Erlinda M Gordon, MD

  Sarcoma Oncology Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erlinda M Gordon, MD

CONTACT

310-552-9999; egordon@sarcomaoncology.com

Victoria Chua-Alcala, MD

CONTACT

310-552-9999; vchua@sarcomaoncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Gene and Cell Therapy/Immunotherapy

Model Details: 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.

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: May 25, 2023
• Study Start: June 7, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)