Trial Outcomes & Findings for Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062) (NCT NCT03099161)

Last Updated: 2019-06-05

Results Overview

DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting \>3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for \>72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) \>3X upper limit of normal (ULN) WITH total bilirubin \>2X ULN with no elevation in alkaline phosphatase (\<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a \>2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing \>25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

Cycle 1 (up to 21 days)

Results posted on

2019-06-05

Participant Flow

This study was planned to have 2 parts: a dose escalation/confirmation phase (Part 1) and an expansion phase (Part 2). The expansion phase was not conducted due to early study termination.

Participant milestones

Participant milestones
Measure	Preladenant 25 mg Twice a Day (BID) Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
Overall Study STARTED	3	4	3
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Preladenant 25 mg Twice a Day (BID) Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
Overall Study Adverse Event	0	0	2
Overall Study Physician Decision	2	0	0
Overall Study Progressive Disease	1	4	1

Baseline Characteristics

Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Cycle 1 (up to 21 days)

Population: All participants who received at least one dose of study treatment in Cycle 1 (21-day Cycle) and were observed for safety or experienced a DLT during Cycle 1

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID n=4 Participants Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by IV infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
Number of Participants With Dose-limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up tp approximately 8 months

Population: All participants who received at least one dose of study treatment

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID n=4 Participants Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by IV infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
Number of Participants Who Experienced at Least One Adverse Event (AE)	3 Participants	4 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to approximately 8 months

Population: All participants who received at least one dose of study treatment

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID n=4 Participants Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by IV infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
Number of Participants Who Discontinued Study Treatment Due to an AE	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to approximately 8 months

Population: All participants who had a baseline scan that showed measurable disease by investigator assessment and who received at least one dose of study treatment

ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 per investigator review. The ORR per RECIST 1.1 for participants is presented.

Outcome measures

Outcome measures
Measure	Preladenant 25 mg BID n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID n=4 Participants Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by IV infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	0.0 Percentage of Participants Interval 0.0 to 70.8	0.0 Percentage of Participants Interval 0.0 to 60.2	0.0 Percentage of Participants Interval 0.0 to 70.8

Adverse Events

Preladenant 25 mg BID

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Preladenant 50 mg BID

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

Preladenant 25 mg BID + Pembrolizumab 200 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Preladenant 25 mg BID n=3 participants at risk Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID n=4 participants at risk Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg n=3 participants at risk Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by IV infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.
Endocrine disorders Inappropriate antidiuretic hormone secretion	33.3% 1/3 • Number of events 1 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/4 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.
Gastrointestinal disorders Dysphagia	33.3% 1/3 • Number of events 1 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/4 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	25.0% 1/4 • Number of events 1 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.
Infections and infestations Urinary tract infection	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/4 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	33.3% 1/3 • Number of events 2 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.
Investigations Liver function test increased	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/4 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	66.7% 2/3 • Number of events 2 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.
Renal and urinary disorders Kidney enlargement	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	25.0% 1/4 • Number of events 1 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.	0.00% 0/3 • Up to approximately 8 months The safety population included all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious adverse event (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Preladenant 25 mg BID n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 50 mg BID n=4 Participants Participants received 50 mg of preladenant administered by oral capsule BID on Days 1 through 21 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Preladenant 25 mg BID + Pembrolizumab 200 mg n=3 Participants Participants received 25 mg of preladenant administered by oral capsule BID on Days 1 through 21 and pembrolizumab 200 mg administered by IV infusion on Day 1 of each 21-day cycle. Participants were to receive up to 35 cycles of study treatment.	Total n=10 Participants Total of all reporting groups
Age, Continuous	61.3 Years STANDARD_DEVIATION 10.8 • n=5 Participants	40.3 Years STANDARD_DEVIATION 16.3 • n=7 Participants	41.3 Years STANDARD_DEVIATION 18.5 • n=5 Participants	46.9 Years STANDARD_DEVIATION 17.0 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 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=4 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=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS=0	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS=1	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Prior Line of Therapy First Line	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Prior Line of Therapy Second Line	0 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Prior Line of Therapy Third Line	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Prior Line of Therapy Fourth Line	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Prior Line of Therapy Fifth Line	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants