Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Death

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunoglobulins

Spartalizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Patients were treated with MIW815 (ADU-S100) via intratumoral injection for 3 weeks followed by one week off in combination with a fixed intravenous dose of PDR001 given once per month

Patients were treated with MIW815 (ADU-S100) via intratumoral injection given once a month in combination with a fixed intravenous dose of PDR001 given once per month

MIW815

PDR001

Nancy Lewis, MD

The purpose of this study was to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001.

This was a Phase Ib, multi-center, open-label study to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of MIW815(ADU-S100) in combination with the PD-1 checkpoint inhibitor PDR001. Two different schedules were explored in two dose escalation groups in accessible cutaneous or subcutaneous lesions. The optional dose confirmation group exploring intratumoral injection of viscerally located lesions was not opened due to the program's early termination.

Group A included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and intratumoral injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle. Group B included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle.

Once the dose and dose schedule had been confirmed, the plan was to open the dose expansion part of the study. However, the expansion phase of the study was not opened to enrollment due to the program's early termination.

The study was comprised of two treatment arms.

Group A included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 intravenous on day 1 of every 28 day cycle and intratumoral injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle.

Group B included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 intravenous on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle.

Once the maximum tolerated dose and/or recommended dose for expansion had been determined, the plan was to open the expansion part of the study. However, the dose expansion phase of the study was not opened to enrollment due to the program's early termination.

Study of the Safety and Efficacy of MIW815 With PDR001 in Patients With Advanced/Metastatic Solid Tumors or Lymphomas

A Phase Ib, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with the combination of MIW815 (ADU-S100) and PDR001

The area under the concentration-time curve extrapolated to infinity (mass\*time/volume)

The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass\* time/volume)

Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass\* time/volume)

The time to reach the maximum observed concentration (time)

The maximum observed concentration (Cmax) following dose administration (mass/volume)

Terminal elimination rate constant (1/time)

Apparent systemic clearance of drug from the plasma (volume x time -1)

Elimination half-life, determined as 0.693/Lambda_z (time)

Apparent volume of distribution during the terminal elimination phase (volume)

Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).

The survival function will be estimated using the Kaplan-Meier product limit method. Median duration, with a two-sided Brookmeyer-Crowley 90% confidence interval and Kaplan-Meier estimates of survival proportions will be provided at specified time points.

The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease

Time To Response is the time from first dose to first documented response (CR or PR). TTR will be summarized

Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due to study indication. Estimates will use Kaplan-Meier method

Induction of TILs in the injected lesion (local PD effect) and in a non-injected lesion (distal PD effect) will be assessed using paired tumor samples at screening and on-treatment.

Novartis Pharmaceuticals

by mouth for 4 days followed by a 3-day rest period every week

LCL161

The study will evaluate the safety of increasing doses of oral LCL161 in patients with solid tumors. It is primarily designed to evaluate the side effects and find the maximum tolerated dose of LCL161.

Safety and Efficacy of LCL161 in Patients With Solid Tumors

A Phase I, Multi-center, Open-label, Dose-escalation Study of Oral LCL161 in Adult Patients With Advanced Solid Tumors

Skin and Connective Tissue Diseases

Melanoma

LHC165 intratumoral injection given alone

LHC165 intratumoral injection given with PDR001 infusion

LHC165

Nehal Parikh, MD

The purpose of this trial was to explore the clinical utility of two investigational agents in patients with advanced cancer.

This was a multi-center, open-label Phase I/Ib study. The primary objectives of the trial were:

* To characterize the safety and tolerability of intratumoral LHC165 in patients with solid tumors as a single agent and in combination with PDR001
* To determine and evaluate the maximum tolerated dose (MTD)/recommended dose (RD) for LHC165 as a single agent and in combination with PDR001

This was a multi-center, open-label Phase I/Ib study. The study consisted of four dose escalation parts and two dose expansion parts testing LHC165 as a single agent or LHC165 in combination with PDR001. The dose escalation parts estimated the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) and were planned to test two different dosing schedules for LHC165 single agent (Group A and B) and LHC165 in combination with PDR001 (Group C and D).

The dose expansion parts of the study were planned to use the MTD/RDE for each the LHC165 single agent (Group E) and LHC165 in combination with PDR001 (Group F), determined in the respective dose escalation parts to assess the activity, safety and tolerability of LHC165 as a single agent or LHC165 in combination with PDR001 in patients with specific types of solid tumors.

The study was terminated due to business reasons. Groups B, D and E were not opened for enrollment.

Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies

A Phase I/Ib, Open-label, Multi-center Dose-escalation and Dose-expansion Study of the Safety and Tolerability of Intra-tumorally Administered LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies

Chondrosarcoma

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Soft Tissue Sarcoma

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Safety and Efficacy of MIW815 With PDR001 in Patients With Advanced/Metastatic Solid Tumors or Lymphomas	NCT03172936	Solid Tumors an...	MIW815 PDR001	18 Years -	Novartis
Safety and Efficacy of LCL161 in Patients With Solid Tumors	NCT01098838	Advanced Solid ...	LCL161	18 Years -	Novartis
Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies	NCT03301896	Solid Tumors	LHC165 PDR001	18 Years -	Novartis
Study of INBRX-109 in Conventional Chondrosarcoma	NCT04950075	Conventional Ch...	INBRX-109 Placebo	18 Years - 85 Years	Inhibrx Biosciences, Inc
Safety and Efficacy of LCL161 in Patients With Solid Tumors	NCT01098838	Advanced Solid ...	LCL161	18 Years -	Novartis
Study of the Safety and Efficacy of MIW815 With PDR001 in Patients With Advanced/Metastatic Solid Tumors or Lymphomas	NCT03172936	Solid Tumors an...	MIW815 PDR001	18 Years -	Novartis
Safety and Efficacy of LCL161 in Patients With Solid Tumors	NCT01098838	Advanced Solid ...	LCL161	18 Years -	Novartis

Spots Global Cancer Trial Database for programmed cell death