OMP-52M51

This is an open-label Phase 1a dose escalation study of single-agent OMP-52M51 in subjects with relapsed or refractory solid tumors. Study includes a dose escalation phase and expansion phase. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and efficacy.

A Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors

A Phase 1 Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors

Apparent half life, AUC, clearance, volume of distribution

OncoMed Pharmaceuticals, Inc.

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Irinotecan

Immunoglobulins

Immunoconjugates

Immunologic Factors

Intravenous infusion to be given with prophylaxis for infusion reactions, evaluating up to five dose cohorts including: 8 mg/kg, 12 mg/kg, 16 mg/kg, 20 mg/kg, and 24 mg/kg.

Intravenous infusion of STI-3258 will be given (one infusion every three weeks).

STI-3258

Mike Royal, MD

This is a phase 1b, open-label, dose-escalation study o STI-3258 administered intravenously in subjects with relapsed or refractory solid tumors.

This is a Phase 1b, open-label, dose-escalation study o STI-3258 administered intravenously in subjects with relapsed or refractory solid tumors including ovarian, breast, lung, esophageal, gastric, hepatocellular and urothelial cancers.

The study will determine any dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), assessing safety and preliminary efficacy using ascending dose cohorts and a conventional 3+3 study design.

To determine DLT and MTD, the design uses a 3+3 ascending dose cohort design evaluating up to five dose cohorts including: 8 mg/kg, 12 mg/kg, 16 mg/kg, 20 mg/kg, 24 mg/kg.

Study to Assess an Anti-Trop2 Antibody Drug Conjugate in Relapsed or Refractory Solid Tumors

A Phase 1B, Dose-Escalation Study of the Safety and Preliminary Efficacy of an Anti-Trop2 Antibody Drug Conjugate (STI-3258) in Patients With Relapsed or Refractory Solid Tumors

Safety as assessed by incidence of adverse events (AEs) by type, frequency, severity, and causality

Safety as assessed by incidence of treatment-emergent AEs (TEAEs) by type, frequency, severity, and causality

Safety as assessed by incidence of serious AEs (SAEs) by type, frequency, severity, and causality

Safety as assessed by incidence of Infusion-related AEs (IrAEs) by type, frequency, severity, and causality

Safety as assessed by incidence of dose-limiting toxicities

To assess the preliminary efficacy of STI-3258 in the treatment of patients with RRSTs based upon Response evaluation criteria in solid tumors (RECIST).

To assess the AUC of STI-3258 in plasma as a measure of exposure to the ADC, STI-3258.

Sorrento Therapeutics, Inc.

Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Cisplatin

* Steady state period:Pazopanib will be given 8 days prior to cisplatin
* Then pazopanib will be given 400 mg, 600 mg or 800 mg/day, daily and cisplatin 60, 75 or 100 mg/m2 , day 1 - 3 weekly, depending of the dose level

cisplatin

Pazopanib

Veronique DIERAS, MD

The aim of this research is to evaluate the potential interest of an association of Pazopanib, a multi-tyrosine kinase inhibitor, and cisplatin.

As cisplatin has marketing approval for several cancers (ovarian, testicle, bladder, esophagus, endometrium, lung, stomach, head and neck cancer (HNC)), and in order to have a rapid evaluation of this combination, we will evaluate the combination in any patient whose tumors is known to be sensible to cisplatin (except tumors at risk of bleeding).

This study is a classical phase 1 trial of pazopanib and 3-weekly cisplatin association. It will allow for optimal dose selection and pharmacokinetic analysis. It is planed to include around 38 patients, enriching the optimal tolerated regimen (OTR) level only with a cohort of triple negative breast cancer patients. If the association is proven to be feasible, we will then move to a specific phase II study in triple negative breast cancer patients.

The main objective of the study is to determine the dose limiting toxicities (DLT) and the optimal tolerated regimen (OTR) which are both safety criteria evaluated upon the NCI CTC-AE system version 4.0.

Efficacy is not the primary objective; however the anti-tumor activity of the pazopanib/cisplatin combination will be carried out by the determination of the objective response rate according to RECIST criteria version 1.1.

The objective response is defined as either a complete response (CR) or partial response (PR), assessed either by CT Scan and/or MRI and/or bone Scan, performed at baseline and every 6 weeks.

This is an open-label, non-randomized, dose escalation and pharmacokinetic, phase I study pazopanib with cisplatin in patients with relapsed or refractory solid tumors (except tumors at risk of bleeding) for whom the selected combined chemotherapy is indicated or is a reasonable option (as per tumor characteristics and previous treatments).

All eligible patients entering the study will receive daily oral pazopanib, supplied as 200 mg aqueous film-coated tablets and intravenous cisplatin every three weeks. Doses of both compounds will be adjusted according to the reached dose level.

The treatment will continue until the development of unacceptable toxicity or evidence of disease progression or until patient's / investigator's decision of withdrawal.

All patients who received at least on dose of the study drug will be followed for survival outcome.

Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors

An Open Label Dose Escalation and Pharmacokinetic Phase I Study With Pazopanib in Combination With Cisplatin (CDDP) Every Three Weeks in Patients With Advanced Solid Tumors

Anti-tumor activity of the pazopanib/cisplatin combination will be carried out by the determination of the objective response rate according to RECIST criteria version 1.1.

The objective of the pharmacokinetics is to investigate the interactions between cisplatin IV and pazopanib

UNICANCER

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Anti-Infective Agents

Antibodies, Monoclonal

Pembrolizumab

Angiogenesis Inhibitors

Lenalidomide

Thalidomide

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Growth Inhibitors

Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide.

Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study.

Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma.

Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer.

For the phase I component of the trial a classic 3 + 3 dose escalation design will be utilized, with a fixed dose of pembrolizumab and an escalating dose of the lenalidomide. The patient population will all have histologically confirmed advanced solid tumor malignancy. The primary endpoint for the phase I component of this protocol will be determining the maximum tolerated dose (MTD) of lenalidomide in combination with pembrolizumab.

The phase II component of this trial will utilize a two stage design, initially enrolling 13 patients, followed by 13 more patients if the early stopping criteria are not met. The target population will include patients with histologically confirmed diagnoses of non-small cell lung carcinoma, regardless of histologic subtype; who have completed one line of standard therapy. The primary endpoint for the phase II component of this protocol will be determining efficacy as measured by progression free survival (PFS)

Phase I The study will plan to enroll 3 patients in an initial cohort, to receive the dose level 1 of lenalidomide (10 mg PO) on days 1-14 of a 21-day cycle, and pembrolizumab (200 mg IV) on day 1. Patients will be evaluated for toxicities after initiation of treatment. If there are no DLTs for the initial 3 patients after one cycle, the next dosing cohort will open, with another 3 patients. Similarly, if the second cohort of patients receives the dose level 2 of lenalidomide (15 mg) for one cycle without DLT, then the third and final cohort will open. When the third cohort testing the dose level 3 of lenalidomide (20 mg) has completed one cycle, the phase I component of the trial will be completed. Standard phase I, 3 + 3 design rules will be utilized as follows: if 1 out of 3 patients experiences a DLT at certain dose level, then 3 more patients will be enrolled at the same level. If 2 out of 6 patients experience DLT at a certain dose level, 3 additional patients are added at the next lower level. Dose reduction is continued until at most 1 of 6 patients experiences DLT. The highest level with at most 1 of 6 patients DLT will be declared MTD. If no dose level achieves this criterion the trial will be discontinued for excess toxicity.

Phase II A pre-treatment (archival) and fresh tumor sample will be needed for participation in trial. PD-L1 expression levels in both samples will be determined to assess the role of chemotherapy on expression level and pattern of this biomarker. Baseline blood samples will be collected for immunologic correlates prior to treatment on Day 1 of Cycle 1 and post treatment at 2, 4, 24 hours. Samples will also be collected prior to treatment on Day 1 of Cycle 2, and at time of progression. Baseline CT scan of the chest and abdomens will be obtained within 30 days prior to the initiation of cycle 1. CT scan with contrast or MRI with contrast of the brain will also be obtained within 30 days prior to the initiation of cycle 1. Time to progression will be measured with disease imaging following every 2 cycles of therapy with a three-day window (+ or -). Patients will continue treatment until disease progression or unacceptable toxicity or two years of therapy. Overall survival will be assessed every 3 months during long term follow up

Phase I/II Study of Lenalidomide Plus Pembrolizumab in Patients With Solid Tumors With Expansion in Non-small Cell Lung Cancer

A Phase I Study of Lenalidomide Plus Pembrolizumab in Patients With Relapsed and/or Refractory Solid Tumors With Phase II Expansion in Non-small Cell Lung Cancer

PD-1 expression will be used to correlate with the treatment response

Amount of CD45, CD3, CD4, CD8 (T cells), CD19 (B cells), CD14, CD16 (monocytes), CD56 (NK cells), CD11c, HLA-DR, CD303, CD66b (myeloid - DCs and granulocytes).

Th1/Tc1 responses ( IFN-g, TNF, IL-2), Th2/Tc1 responses (IL-4, IL-5, IL-10), pro-inflammatory innate responses (IFN-α, IL-1β, IL-6, IL-17), homeostatic lymphocyte expansion (IL-7, IL-15), and chemotaxis of immune cells (IP-10, MCP-1, MIP-1α, MIP-1β, RANTES) will be measured

CD107A expression after 2 hour co-culture with the EBV-transformed B cell line, 721.221, without and with rituximab (ADCC conditions).

Activation markers will include CD69, CD25, HLA-DR, IL-15Ra, perforin, Ki67, NKp44, CD57

Expression of genes involved in immune responses

number of patients that overcome the resistance of previous anti-pD-1 therapy

Differentiation status of CD4 and CD8 T cells (naïve/effector memory/central memory/regulatory/delta-gamma TCR) as defined by: CD62L, CD45RA, CD127, CD25.

Merck Sharp & Dohme LLC

Celgene

Fox Chase Cancer Center

Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide.

Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study.

Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma.

Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer.

Pembrolizumab, Lenalidomide

Age, Categorical

Sex: Female, Male

White Non-Hispanic

Black or African American

Race/Ethnicity, Customized

United States

Region of Enrollment

Hossein Borghaei, DO, MS

Experimental: Pembrolizumab, Lenalidomide

Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

To Determine the Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With a Fixed Dose of Pembrolizumab in Subjects With Relapsed and/or Refractory Solid Tumors.

To Determine Efficacy as Measured by Progression Free Survival (PFS) in Non-small Cell Lung Cancer Patients

Assess Antitumor Activity of the Combination as Measured by Objective Response Rate (ORR)

Assessment of PD-L1 Expression by Immunohistochemistry

Proportions of Blood Immune Cells by Flow Cytometry

Assesment of Cytokine Profiles Using Luminex

Determine Specific NK Cell Responses by NK Degranulation Assay by Flow Cytometry

Assessment of Activation Markers on Immune Cells by Flow Cytometry

Determine Immune Composition of Tumors Using PanCancer Immune Profiling Panel by Nanostring Technology

From Patients That Were Previously Treated With an Anti-PD1 Antibody, we Will Determine Resistance Overcome Due to the Treatment With Combination Assessed by Overall Response Rate.

Determine Specific T Cell Responses by Determining Differentiation Status of T Cells by Flow Cytometry

Overall Study

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Communicable Diseases

Carcinoma, Transitional Cell

Ovarian Neoplasms

Urinary Bladder Neoplasms

Carcinoma, Pancreatic Ductal

Virus Diseases

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Tumor Virus Infections

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Fallopian Tube Diseases

Carcinoma, Ductal

Adenocarcinoma

Pancreatic Neoplasms

Pancreatic Diseases

Ovarian Cancer

Pancreatic Cancer

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Azacitidine

Cc-486

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability. Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4.

CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability

ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m\^2

CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability

CC-486

Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4.

ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m\^2

ABI-007

Gordan Bray, M.D., Ph.D

The purpose of the study is to evaluate the safety and to define the Maximal Tolerated Dose (MTD) or the Maximal Administered Dose (MAD) of oral azacitidine as a single agent and in combination with carboplatin (CBDCA) or paclitaxel protein bound particles (ABI-007,ABX) in subjects with relapsed or refractory solid tumors.

A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors

An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity.

Maximum observed concentration in plasma (Cmax)

Area under the concentration-time curve (AUC)

Change from baseline (Cycle 1 Day 1 pre-dose) in DNA methylation (global and gene-specific assays) in whole blood and tumor tissue (as available in Part 1)

Reduction from baseline (Cycle 1 Day 1 predose) in DNMT1 protein levels in tumor tissue (as available in Part 1)

Response and progression were evaluated using the RECIST 1.1 criteria. Treatment response includes both complete response and partial response.

* Complete response-disappearance of all lesions
* Partial response-30% decrease in the sum of diameters of target lesions from baseline

Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first.

Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors	NCT01778439	Relapsed or Ref...	OMP-52M51	18 Years - 90 Years	Mereo BioPharma
Study to Assess an Anti-Trop2 Antibody Drug Conjugate in Relapsed or Refractory Solid Tumors	NCT05060276	Relapsed Solid ... Refractory Canc... Solid Tumor, Ad...	STI-3258	18 Years -	Sorrento Therapeutics, Inc.
A Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors	NCT01778439	Relapsed or Ref...	OMP-52M51	18 Years - 90 Years	Mereo BioPharma
Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors	NCT01165385	Solid Tumors Metastatic Canc...	cisplatin Pazopanib	18 Years -	UNICANCER
Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors	NCT01165385	Solid Tumors Metastatic Canc...	cisplatin Pazopanib	18 Years -	UNICANCER
A Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors	NCT01778439	Relapsed or Ref...	OMP-52M51	18 Years - 90 Years	Mereo BioPharma
Phase I/II Study of Lenalidomide Plus Pembrolizumab in Patients With Solid Tumors With Expansion in Non-small Cell Lung Cancer	NCT02963610	Relapsed or Ref... Nonsmall Cell L...	Lenalidomide Pembrolizumab	18 Years -	Fox Chase Cancer Center
A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors	NCT01478685	Urinary Bladder... Carcinoma, Tran... Ovarian Neoplas... Fallopian Tube ... Peritoneal Neop... Carcinoma, Non-... Carcinoma, Panc... Tumor Virus Inf...	CC-486 Carboplatin ABI-007	18 Years -	Celgene
A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors	NCT01478685	Urinary Bladder... Carcinoma, Tran... Ovarian Neoplas... Fallopian Tube ... Peritoneal Neop... Carcinoma, Non-... Carcinoma, Panc... Tumor Virus Inf...	CC-486 Carboplatin ABI-007	18 Years -	Celgene

Spots Global Cancer Trial Database for relapsed or refractory solid tumors