Trial Outcomes & Findings for Oral Decitabine and Tetrahydrouridine as Epigenetic Priming for Pembrolizumab-Mediated Immune Checkpoint Blockade in Patients With Inoperable, or Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancers and Esophageal Carcinomas (NCT NCT03233724)

Last Updated: 2023-05-31

Results Overview

Overall response rate was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to determine if the combination of decitabine and tetrahydrouridine is associated with a response rate which exceeds that of Pembrolizumab alone in participants who have programmed death-ligand 1 (PD-L1) expression of at least 50% and those who do not. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Every 10 weeks (± 1 week) until disease progression or unacceptable toxicity or off study criteria is met. Longest participant on study 11 months.

Results posted on

2023-05-31

Participant Flow

Participant milestones

Participant milestones
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.	Enrolled to Revised Dose Level 1 But Not Treated Participants who were enrolled but not treated.
Phase I Dose Escalation STARTED	2	2	4	1
Phase I Dose Escalation COMPLETED	1	1	1	0
Phase I Dose Escalation NOT COMPLETED	1	1	3	1
Phase II Dose Expansion STARTED	0	0	0	0
Phase II Dose Expansion COMPLETED	0	0	0	0
Phase II Dose Expansion NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.	Enrolled to Revised Dose Level 1 But Not Treated Participants who were enrolled but not treated.
Phase I Dose Escalation Removed from protocol prior to treatment due to rapidly progressive esophageal obstruction.	0	0	0	1
Phase I Dose Escalation Best interest of participant	1	1	1	0
Phase I Dose Escalation Physician Decision	0	0	1	0
Phase I Dose Escalation Delay >3 weeks on treatment	0	0	1	0

Baseline Characteristics

Oral Decitabine and Tetrahydrouridine as Epigenetic Priming for Pembrolizumab-Mediated Immune Checkpoint Blockade in Patients With Inoperable, or Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancers and Esophageal Carcinomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks n=4 Participants Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.	Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks Phase 1, Arm 1, Dose Escalation, Revised Dose Level -1. Participants received Decitabine 0.17 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.	Enrolled to Revised Dose Level 1 But Not Treated n=1 Participants Participants who were enrolled but not treated.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	—	1 Participants n=21 Participants	6 Participants n=10 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants	3 Participants n=10 Participants
Age, Continuous	58.2 years STANDARD_DEVIATION 11.74 • n=5 Participants	80.85 years STANDARD_DEVIATION 11.53 • n=7 Participants	49.62 years STANDARD_DEVIATION 10.02 • n=5 Participants	—	62.4 years STANDARD_DEVIATION 0 • n=21 Participants	59.9 years STANDARD_DEVIATION 15.34 • n=10 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	—	0 Participants n=21 Participants	4 Participants n=10 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	—	1 Participants n=21 Participants	5 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	0 Participants n=21 Participants	1 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	—	1 Participants n=21 Participants	8 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	0 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	—	1 Participants n=21 Participants	5 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants	0 Participants n=10 Participants
Region of Enrollment United States	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	—	1 participants n=21 Participants	9 participants n=10 Participants

PRIMARY outcome

Timeframe: Every 10 weeks (± 1 week) until disease progression or unacceptable toxicity or off study criteria is met. Longest participant on study 11 months.

Population: 1/9 participants did not receive any therapy.

Outcome measures

Outcome measures
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks n=4 Participants Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.
Overall Response Rate Complete Response	0 Participants	0 Participants	0 Participants
Overall Response Rate Partial Response	0 Participants	0 Participants	0 Participants
Overall Response Rate Stable Disease	0 Participants	0 Participants	1 Participants
Overall Response Rate Progressive Disease	0 Participants	1 Participants	1 Participants
Overall Response Rate Unevaluable for response	2 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Within the first 6 weeks (two cycles)

Population: 1/9 participants did not receive any therapy.

Maximum Tolerated Dose (MTD) is the maximum dose at which fewer than one-third of participants experience dose limiting toxicity (DLT) within the first 6 weeks (two cycles) of decitabine and tetrahydrouridine therapy. If one of three patients at any given dose level experiences DLT, up to three additional patients will be treated at this dose level. If only one of six patients exhibit DLT, subsequent patients will be enrolled into the next higher dose level. As soon as two patients at any given dose level develop DLT, no additional patients will be entered at that level. Subsequent patients will be accrued into the preceding dose level; if DLT is observed in less than two of six patients treated at this lower level, this dose will represent maximum tolerated dose (MTD). A DLT is any Grade 3 or greater toxicity that cannot be attributed to a cause other than study treatment during the first two cycles of Course 1 of therapy such as disease progression or intercurrent illness.

Outcome measures

Outcome measures
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks n=4 Participants Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.
Maximum Tolerated Dose (MTD) of Decitabine	NA mg/kg MTD was not found due to the termination of the study.	NA mg/kg MTD was not found due to the termination of the study.	NA mg/kg MTD was not found due to the termination of the study.

PRIMARY outcome

Timeframe: Within the first 6 weeks (two cycles)

Population: Within the first 6 weeks (two cycles)

Outcome measures

Outcome measures
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks n=4 Participants Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.
Maximum Tolerated Dose (MTD) of Tetrahydrouridine	NA mg/kg MTD was not found due to the termination of the study.	NA mg/kg MTD was not found due to the termination of the study.	NA mg/kg MTD was not found due to the termination of the study.

SECONDARY outcome

Timeframe: Baseline and post-treatment after one course of therapy (Week 10 +/- one week)

Population: This outcome measure was not evaluated and was to be performed in bulk. No assays were performed due to the pandemic. Participants could not travel to the National Institutes of Health (NIH) to have samples drawn.

Peripheral blood will be collected to correlate changes in circulating tumor cells with clinical response. CTCs will be assessed using ferrofluidic enrichment and multi-parameter flow cytometric detection. Baseline and post-treatment specimen collection after one course of therapy (Week 10 +/- one week).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and post-treatment after one course of therapy (Week 10 +/- one week)

Peripheral blood mononuclear cells (PBMC) will be assessed using multiparameter flow cytometry for immune subsets including but not necessarily limited to Tregs, myeloid-derived suppressor cells (MDSC), effector and exhausted cluster of differentiation 4 (CD4+), cytotoxic T lymphocytes (CD8+) T cells, and cluster of differentiation 14 (CD14 +) monocytes. Assessment will include functional markers, i.e., programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), cluster of differentiation 152 (CTLA-4), human leukocyte antigen (HLA) membrane heterodimeric glycoproteins (-DR) and/or cluster of differentiation 40 (CD40). Baseline and post-treatment specimen collection after one course of therapy (Week 10 +/- one week).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and post-treatment after one course of therapy (Week 10 +/- one week)

Population: This outcome measure was not done because 1 participant declined biopsy due to the pandemic. And one participant did not have adequate tissue to evaluate. All other participants did not have biopsies.

Portions of biopsy materials will be sent for frozen section or permanent section confirmation of malignancy, i.e., non-small cell lung cancers (NSCLC), esophageal carcinomas (Esc), malignant pleural mesothelioma (MPM) cells, and percent viable tumor cells. All of the analyses are predicated on acquisition of sufficient materials.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and post-treatment after one course of therapy (Week 10 +/- one week)

Tissue will be processed for focused gene, endogenous retroviral and microRNA expressions, and DNA methylation signatures using quantitative reverse-transcription polymerase chain reaction (RT-PCR), nanostring, pyrosequencing and digital droplet PCR techniques. Isolate serum for focused methylation analysis. If sufficient tissue is available, another portion will be imbedded in paraffin for subsequent immunostaining experiments, focusing on expression of genes focusing on those proteins encoded by genes that have been identified to be clearly activated by epigenetic therapy. If sufficient materials are present, additional more comprehensive analyses including multiplex immunohistochemistry analysis of tumor microenvironment may be performed with the focus of materials from participants treated at the maximum tolerated dose. All of the analyses are predicated on acquisition of sufficient materials.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively.

Population: 1/9 participants did not receive any therapy.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks n=4 Participants Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	2 Participants	2 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First two cycles of Course 1 of therapy

Population: 1/9 participants did not receive any therapy.

A DLT is any Grade 3 (severe) or greater toxicity that cannot be attributed to a cause other than study treatment during the first two cycles of Course 1 of therapy such as disease progression or intercurrent illness.

Outcome measures

Outcome measures
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) n=2 Participants Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks n=4 Participants Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.
Number of Participants With a Dose Limiting Hematologic Toxicity (DLT)	2 Participants	2 Participants	1 Participants

Adverse Events

Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT)

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT)

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) n=2 participants at risk Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level 1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) q week with Pembrolizumab infusion q3weeks	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) n=2 participants at risk Phase 1, Arm 1, Dose Escalation, ORIGINAL Dose Level -1: Participants received Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) q week. Participants received Pembrolizumab infusion q3weeks.	Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks n=4 participants at risk Phase 1, Arm 1, Dose Escalation, Revised Dose Level 1. Participants received Decitabine 0.21 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.	Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks Phase 1, Arm 1, Dose Escalation, Revised Dose Level -1. Participants received Decitabine 0.17 mg/kg + Tetrahydrouridine 10mg/kg TW weekly x 2 weeks q 3 weeks. Participants received pembrolizumab infusion q 3weeks.
Blood and lymphatic system disorders Febrile neutropenia	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	— 0/0 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/2 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	— 0/0 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.
Investigations Lymphocyte count decreased	50.0% 1/2 • Number of events 5 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	— 0/0 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.
Investigations Neutrophil count decreased	100.0% 2/2 • Number of events 3 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	25.0% 1/4 • Number of events 5 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	— 0/0 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.
Infections and infestations Sepsis	0.00% 0/2 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	— 0/0 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.
Infections and infestations Skin infection	0.00% 0/2 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	50.0% 1/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	— 0/0 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.
Investigations White blood cell decreased	100.0% 2/2 • Number of events 3 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.	— 0/0 • Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. 1/9 participants did not receive any therapy.

Other adverse events

Additional Information

Dr. David S. Schrump

National Cancer Institute

Phone: 240-760-6239

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place