Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Liposarcoma

Chondrosarcoma

Liposarcoma, Myxoid

Chondrosarcoma, Mesenchymal

Neoplasms, Adipose Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Neoplasms, Connective Tissue

Myxoid Liposarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Sirolimus

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule

sirolimus and cyclophosphamide

Hans Gelderblom, Prof

Chondrosarcoma and liposarcoma consists of different subtypes with a wide range of patient survival. Current treatment options consist of wide surgical resection, however for patients with a local recurrence or metastatic disease the outcome is poor. New treatment options being evaluated and mouse models show in vivo that mammilian target of rapamycin (mTOR) inhibition can prevent tumour growth. mTOR is an kinase that is present in two complexes and thereby activates multiple pathways. Aberrant mTOR signalling is known to be involved in cancer cell survival. Several clinical studies for patients with bone or soft tissue sarcoma treated with mTOR inhibitors have been conducted and they show promising results. From these studies the investigators can conclude that the combination of an mTOR inhibitor with cyclophosphamide shows promising results in chondrosarcoma. With the lack of other treatment options for unresectable and metastatic chondrosarcoma or myxoid liposarcoma the Eurosarc consortium (www.eurosarc.eu) decided to treat these patients in a standardised way according to a common protocol with the combination of sirolimus and cyclophosphamide using the growth modulation index for evaluation in the current clinical study protocol.

Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

A Phase 2, Single Arm, Multi Center Trial Evaluating the Efficacy of the COmbination of Sirolimus and cYclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and chOndrosarcoma

GMI: Time to progression during sirolimus/cyclophosphamide treatment (TTP2) divided by time to progression before start of this treatment TTP1

Leiden University Medical Center

Prof A.J. Gelderblom

Symptoms and General Pathology

Death

Antibodies

Immunoglobulins

INBRX-109

Placebo

Study Director, -Inhibrx

Clinical Trials Office - All Mayo Locations

Mahesh Seetharam, MD

Bianca Bacaltos, CRS

Victoria Wang, MD

Victoria Chua-Alcala

Sant P Chawla, MD

Natalie Frisbie

Breelyn Wilky, MD

Steven Attia, MD

Martha Fuentes

Andrew Brohl, MD

Hannah Knott

Seth Pollack, MD

Clinical Trials Office

Marta Batus, MD

Teena Davis-Vandaele

Katie Keeler

Mohammed Milhem, MD

Christian Meyer, MD

Alex Thompson

Sarcoma Research

Andrew Wagner, MD

Kristen Finn

Gregory Cote, MD

Irina Verdiyan

Rashmi Chugh, MD

Jolene Steibel

Brian Van Tine, MD

Kathryn Bartz

Kirsten Leu, MD

Jacob DuBien

Garrett Wasp, MD

Haley Phelan

Ciara Kelly, MD

Soren Evers

Richard Riedel, MD

Heather Keaney

Dale Shepard, MD

Melissa Yarbrough, RN

Minh Phan, MD

Ray Jackson

Lara Davis, MD

Colin Burns

Atrayee Basu-Mallick, MD

Amy Rose

Melissa Burgess, MD

Kathy Taylor

Elizabeth Davis, MD

Tiffany Thomas, BSN, RN

Jade Homsi, MD

Jaqueline Rios

Anthony Conley, MD

Carrie Friedman

Alexander Spira, MD

Roxanne Moore

Lee Cranmer, MD

Nimit Singhal, MD

Peter Grimison, MD

Vladimir Andelkovic, MD

Justine Retailleau

Maud Toulmonde, MD

Julien Timmins

Jean-Yves Blay, MD

Annick Pelletier

Florence Duffaud, MD

Yasmine Bouredjoul

Axel Le Cesne, MD

Miriam Hammermeister

Peter Reichardt, MD

Albert Kollak

Peter Hohenberger, MD

Amy Mahon

Doherty, MD

Michela Pierini

Emanuela Palmerini, MD

Simone Morabito

Sandra Aliberti, MD

Matilde Ingrosso

Silvia Stacchiotti

Francesca Delmonte

Giacomo Baldi, MD

Teresa Grassani

Bruno Vincenzi, MD

Fokje de Zwart

Jacco de Haan, MD

Margret den Hollander

Andre (Hans) Gelderbloom, MD

Carlos Fernandez

Claudia Valverde, MD

Luis Gonzalez Gomez

Ana Sebio Garcia, MD, PhD

Helena Olivera Frade

Antonio Casado, MD

Angel Flores

Javier Martin-Broto, MD, PhD

Mayte Giralt

Roberto Diaz Beveridge, MD

Tara Searle

Sandra Strauss, MD

Kowsar Ahmed

Robin Jones, Prof.

Monika Burek

Alexander Lee, MD

harriet Bradford White

Sarah Pratap, MD

Clinical Lead

Randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients.

This is a randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients. INBRX-109 is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).

INBRX-109 and placebo arms are in parallel. Patients on placebo are allowed to cross-over to open-label INBRX-109 at time of disease progression.

Study of INBRX-109 in Conventional Chondrosarcoma

A Randomized, Blinded, Placebo-controlled, Phase 2 Study of INBRX-109 in Unresectable or Metastatic Conventional Chondrosarcoma

QoL per EORTC QLQ-C30, EQ-5D-5L, PGI-C, PGI-S

Evaluate the relationship between potential predictive response biomarkers and efficacy of INBRX-109

evaluate the anticancer efficacy of INBRX-109 as measured by PFS (by Investigator assessment) for crossover population after treatment with INBRX-109

evaluate the anticancer efficacy of INBRX-109 as measured by ORR (by Investigator assessment) for crossover population after treatment with INBRX-109

Progression-free survival per RECISTv1.1 will be determined.

Tumor response will be determined by RECISTv1.1.

PFS per RECISTv1.1, by Investigator assessment, comparing INBRX-109 and placebo.

measured by DCR per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo

evaluate duration of response (DOR) per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo

Adverse events will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

AUC0-inf, AUC0-last, AUC0-21d, Cmax, Ctrough, Tmax will be estimated using a standard non- Sponsor: Inhibrx, Inc. Version 5.0 (Amendment 4) Protocol Number: Ph2 INBRX-109 SA CS 28-Feb-2023 Page 41 of 113 CONFIDENTIAL Objective Endpoint compartmental method as the data allow. Other PK parameters (λz, t1/2, Vd, CL, and accumulation ratios RCmax, RCtrough)

Frequency of anti-drug antibodies against INBRX-109 will be determined.

Inhibrx Biosciences, Inc

Ivosidenib

Enzyme Inhibitors

Taken continuously until BICR-confirmed disease progression, unacceptable toxicity, confirmed pregnancy, death, withdrawal of consent, lost to follow-up, or the Sponsor ends the study (estimated average treatment duration of two years).

Taken continuously until BICR-confirmed disease progression, unacceptable toxicity, confirmed pregnancy, death, withdrawal of consent, lost to follow-up, or the Sponsor ends the study (estimated average treatment duration of two years). Participants randomized to the placebo arm who experience BICR-confirmed disease progression and meet the crossover eligibility criteria will be given the opportunity to cross over and receive ivosidenib.

Provided as tablets, taken orally as two 250mg tablets once daily.

Ivosidenib 500mg

Provided as tablets, taken orally once daily.

Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department

Study CL3-95031-007 (CHONQUER) is a Phase 3, international, multicenter, double-blind, randomized, placebo-controlled study of orally administered ivosidenib. Participants are required to have a histopathological diagnosis consistent with isocitrate dehydrogenase-1 (IDH1) gene-mutated, locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection. IDH1 mutant status will be determined during pre-screening/screening phase. Participant must have radiographic progression/recurrence of disease according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and have received 0 to 1 prior systemic treatment regimen in the advanced/metastatic setting for conventional chondrosarcoma. The primary endpoint is progression-free survival (PFS) in Grades 1 and 2 participants. Key secondary endpoints are PFS in all randomized participants, overall survival (OS) in Grades 1 and 2 participants, and OS in all randomized participants.

Participants who meet enrollment criteria will be randomized 1:1 to receive oral ivosidenib 500mg once daily, or a matching placebo once daily.

Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled Study of Ivosidenib in Participants ≥18 Years of Age With Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

* used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

* sponsored by Servier
* with a first patient enrolled as of 1 January 2004 onwards
* for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

From randomization until BICR confirmed progressive disease or death due to any cause, whichever occurs first

From randomization until confirmed CR or PR

The time from date of first documented confirmed CR or confirmed PR to date of first documented disease progression or death due to any cause.

The time from the date of randomization to date of first documented confirmed complete response (CR) or confirmed partial response (PR).

The EORTC-QLQ-C30 contains 30 items across 5 functional scales, 9 symptom scales and a global health status. Raw scores are converted to scales ranging from 0 - 100. For the functional scales and global health status, the higher score represents the better functioning or global health status; for the symptom scales, the higher score represents an increase in symptoms.

The 5-level EQ-5D-5L scores range from 5 to 25 with a higher number representing a worse health status.

The PROMIS Item Bank v1.0 Physical Function with Mobility Aid - Short Form questionnaire score ranges from 1 "Unable to do" to 5 "Can do without a problem" for each capability.

Institut de Recherches Internationales Servier

Servier Bio-Innovation LLC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma	NCT02821507	Conventional Ch... Myxoid Liposarc... Mesenchymal Cho... Dedifferentiate...	sirolimus and c...	18 Years -	Leiden University Medical Center
Study of INBRX-109 in Conventional Chondrosarcoma	NCT04950075	Conventional Ch...	INBRX-109 Placebo	18 Years - 85 Years	Inhibrx Biosciences, Inc
Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen	NCT06127407	Locally Advance...	Ivosidenib 500m... Placebo	18 Years -	Servier

Spots Global Cancer Trial Database for conventional chondrosarcoma