PDR001 + Panobinostat for Melanoma and NSCLC

NCT03982134 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 201904832
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research study is to find the dose of the study drug PDR001 that, when given in combination with the drug Panobinostat, results in the best outcomes for metastatic melanoma and non-small cell lung cancer (NSCLC)

Conditions

Melanoma; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability of PDR001 in combination with panobinostat in determining a recommended Phase II dose

  The recommended Phase 2 dose will be determined by using a 3 + 3 design with 1 dose escalation and 2 dose deescalation cohorts. Safety assessments will consist of monitoring and recording all adverse events, including serious adverse events, the monitoring of hematology, chemistry, ECG and the regular monitoring of vital signs, thyroid function, pregnancy and physical exam including weight and performance status.

  Initiation of treatment up to 2 years

Secondary Outcomes (4)

• Incidence of dose limiting toxicities (DLTs) using CTCAE, Version 5.0

  Initiation of treatment up to 2 years

• Progression free survival (PFS) per RECIST 1.1

  Initiation of treatment up to 2 years

• Overall survival (OS)

  Initiation of treatment up to 2 years

• Overall Response Rate (ORR) per RECIST 1.1

  Initiation of treatment up to 2 years

Study Arms (1)

PDR001 with Panobinostat

EXPERIMENTAL

All enrolled patients will be treated with a combination of PDR001 at 400mg every 4 weeks and panobinostat. Dose and frequency of Panobinostat will vary depending upon the dose-level cohort of the study participants. Each participant will be assigned to a particular dose-level cohort.

Drug: PDR001; Drug: Panobinostat

Interventions

PDR001 DRUG

PDR001 is a humanized IgG4 antibody

Also known as: spartalizumab

PDR001 with Panobinostat

Panobinostat DRUG

Panobinostat is a Histone deacetylase inhibitor (HDACi).

Also known as: LBH589 lactate

PDR001 with Panobinostat

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent prior to any screening procedures.
• Age 18 years or older.
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests
• Able to swallow and retain oral medication Panobinostat
• Histologically or cytologically confirmed diagnosis of melanoma or NSCLC
• ECOG performance status of 0-2
• Patients with melanoma and NSCLC must have progressed clinically as determined by the treating physician on a prior line of anti-PD-1/PD-L1 therapy. If they have received more than one line of prior therapy, the last treatment must be with an anti-PD-1/PDL-1 inhibitor, alone or in combination with another systemic therapy (e.g. chemotherapy, CTLA4 inhibitor).
• Patients with NSCLC who are known to have targetable genomic alterations (including EGFR exon 19 deletion or L858R substitution, ALK rearrangement, ROS1 fusion, NTRK 13 fusions, BRAF V600 mutation), must have progressed on or could not tolerate FDA approved targeted therapy for the alterations mentioned above, in addition to progressed on PD-1/L1 Checkpoint blockade to be eligible for the study. Patients with Melanoma who are known to have BRAF V600 mutation must have progressed on or could not tolerate BRAF-targeted therapy with or without MEK inhibitor in addition to PD-1/PD-L1 checkpoint inhibitor to be eligible for the study.

You may not qualify if:

• Patients eligible for this study must not meet any of the following criteria:
• Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the prior 2 weeks. Patients with residual symptoms that are either controlled or improving after treatment will be allowed to participate in the study.
• History of severe hypersensitivity reactions to other mAbs
• Prior treatment with an HDAC inhibitor
• Patients who meet the following laboratory criteria:
• Hematology:
• Neutrophil count of \</=1500/mm3
• Platelet count of \</=100,000/mm3
• Hemoglobin \< 8 g/dL (Transfusion support is allowed to meet the eligibility)
• Biochemistry:
• AST/SGOT and ALT/SGPT \>3 x upper limit of normal (ULN) or \> 5.0 x ULN if the transaminase elevation is due to disease involvement
• Serum bilirubin \> 1.5 x ULN
• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) \</=40 mL/min
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade \>/= 2), uncontrolled hypertension or clinically significant arrhythmia

Sponsors & Collaborators

• Muhammad Furqan: lead
• Novartis Pharmaceuticals: collaborator

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

spartalizumab; Panobinostat

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Muhammad Furqan, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

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: Clinical Assistant Professor

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 11, 2019
• Study Start: September 1, 2019
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2022
• Last Updated: October 4, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share