Study of MK-1697 in Participants With Advanced Solid Tumors (MK-1697-001)

NCT03515824 | Terminated Phase 1 Results

• 2 other identifiers: 1697-001MK1697-001
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and preliminary efficacy of MK-1697. There are 2 parts in this study: dose escalation to determine the recommended phase 2 dose (RP2D) and confirm the RP2D (Part A) and cohort expansion to determine preliminary efficacy in participants with colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC) (Part B). No formal hypothesis testing will be done in this study.

Conditions

Neoplasms; Colorectal Neoplasms; Head and Neck Neoplasms

Keywords

Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); PD-1; PDL1; PD-L1

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1

  The following toxicities were considered a DLT, if assessed as related to study treatment: Grade (Gr) 4 non-hematologic toxicity (T); Gr 4 hematologic T for ≥7 days; Gr 4 thrombocytopenia; Gr 3 thrombocytopenia with bleeding; ≥Gr 3 non-hematologic clinical AE except fatigue for ≤3 days, Gr 3 nausea, vomiting, or diarrhea for \>72 hours despite anti-emetics/diarrheals, or other supportive care; Gr 3 rash without corticosteroids/anti-inflammatory agents use per standard of care; Gr 3/4 non-hematologic laboratory value if: medical intervention is required, abnormality leads to hospitalization, persists for \>1 week, or abnormality results in drug-induced liver injury; Gr 3 or 4 febrile neutropenia; treatment-related T causing discontinuation; inability to administer ≥75% of planned dose due to drug-related tolerability; Gr 5 T; delay in Cycle 2 start by \>2 weeks due to T. Pool-adjacent violators algorithm was used to estimate DLT rate \& Bayesian method for 80% confidence intervals (CIs).

  Up to 21 days of Cycle 1 (cycle length = 21 days)

• Number of Participants Who Experienced At Least One Adverse Event (AE)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced at least one AE were presented.

  Up to approximately 9 months

• Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued study intervention due to an AE were presented.

  Up to approximately 8 months

Secondary Outcomes (6)

• Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 18 months (through End of Trial data cut-off 18 Feb 2020)

• Objective Response Rate (ORR) Per Modified Response Evaluation Criteria In Solid Tumors Version 1.1 for Immune-based Therapeutics (iRECIST)

  Up to approximately 18 months (through End of Trial data cut-off 18 Feb 2020)

• Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697

  Cycle 1-3: Days 1, 2 (only Cycle 1), 3, 8, 15 - predose and postdose at 10 minutes, 2 hours (cycle length = 21 days)

• Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697

  Cycles 1, 2, and 3: predose, 10 minutes and 2 hours post-dose (cycle length = 21 days)

• Maximum Serum Concentration (Cmax) of MK-1697

  Cycle 1-3: Days 1, 2 (only Cycle 1), 3, 8, 15 - predose and postdose at 10 minutes, 2 hours (cycle length = 21 days)

Study Arms (4)

Part A: MK-1696 20 mg

EXPERIMENTAL

Participants received 20 mg of MK-1697 by intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).

Biological: MK-1697

Part A: MK-1697 65 mg

EXPERIMENTAL

Participants received 65 mg of MK-1697 by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).

Biological: MK-1697

Part A: MK-1697 200 mg

EXPERIMENTAL

Participants received 200 mg of MK-1697 by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).

Biological: MK-1697

Part B: Expansion Cohort

EXPERIMENTAL

Participants with select tumor types were to receive MK-1697 at the RP2D by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).

Biological: MK-1697

Interventions

MK-1697 BIOLOGICAL

Administered by IV infusion on Day 1 of each 21-day cycle

Part A: MK-1696 20 mg; Part A: MK-1697 200 mg; Part A: MK-1697 65 mg; Part B: Expansion Cohort

Eligibility Criteria

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

You may qualify if:

• For Part A; has a histologically- or cytologically-confirmed advanced/metastatic solid tumor and has received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit
• For Part B: has 1 of the following histologically or cytologically confirmed tumor types that are anti-programmed cell death protein 1 (anti PD-1)/anti-programmed death-ligand 1 (anti PD-L1) treatment naive:
• CRC originating in either the colon or rectum that is locally advanced unresectable or metastatic (ie, Stage IV) and that has received, and progressed on, all available standard-of-care therapies including fluoropyrimidine, oxaliplatin, and irinotecan
• HNSCC that is considered incurable by local therapies. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Participants may not have a primary tumor site of nasopharynx (any histology). Also, participants must have progressed after receiving platinum-containing systemic therapy
• Has measurable disease by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
• Has an evaluable baseline tumor sample (either a recent or archival) for analysis
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has central venous access (eg, portacath, Hickman line, or peripherally inserted central catheter \[PICC\] line) currently inserted or be considered medically fit for and willing to undergo the insertion of such a device
• Is not pregnant or breastfeeding
• Female participants of childbearing potential must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment
• Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period

You may not qualify if:

• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years with the exception of participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in-situ cancers
• Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody and/or components of the study treatment
• Has an active infection requiring therapy
• Has a history of interstitial lung disease
• Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has known human immunodeficiency virus (HIV) and/or Hepatitis B or C infections, or known to be positive for Hepatitis B antigen/Hepatitis B virus deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation, make administration of the study treatments hazardous, or make it difficult to monitor adverse effects in the opinion of the treating investigator
• Has a history or current evidence of severe cardiovascular disease, ie, arrhythmias requiring chronic treatment, congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) or symptomatic ischemic heart disease.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
• Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered
• Has known microsatellite instability (MSI) high or mismatch repair genes (MMR) deficient colorectal cancer. If a participant's MSI status is unknown, a paired blood sample for MSI in addition to biomarker testing is required to determine MSI status retrospectively (for the CRC expansion cohort only)
• Has a positive pregnancy test within 72 hours before the first dose of study treatment

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Scientia Clinical Research ( Site 0100)

Randwick, New South Wales, 2031, Australia

Location

Queen Mary Hospital ( Site 0200)

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Neoplasms; Colorectal Neoplasms; Head and Neck Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Limitations and Caveats

The study was terminated due to business reasons.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 4, 2018
• Study Start: August 13, 2018
• Primary Completion: February 18, 2020
• Study Completion: February 18, 2020
• Last Updated: March 9, 2021
• Results First Posted: February 12, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

AU (1); HK (1)