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Colorectal Cancer (CRC)Phase 1NCT02646748

Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors

A Phase 1 study testing Pembrolizumab, itacitinib and INCB050465 in people with Colorectal Cancer (CRC) and Endometrial Cancer, run by Incyte Corporation at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, multicenter, Phase 1b platform study in subjects with advanced or metastatic solid tumors (Part 1a) and subjects with selected solid tumors (Part 1b and Part 2). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, itacitinib and INCB050465
Could I receive a placebo?
No, everyone receives an active treatment
How many people
159 participants
Where
17 sitesUnited States
Study dates
25 Jan 2016to 20 Nov 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age 18 years or older.
  • Willingness to provide written informed consent for the study.
  • Has a core or excisional baseline tumor biopsy specimen available or willingness to undergo a pre study treatment tumor biopsy to obtain the specimen.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Presence of measureable disease based on RECIST v1.1
  • For Part 1a: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
Show all 15Show fewer
  • For Part 1b: Subjects with histologically or cytologically confirmed advanced or metastatic endometrial cancer, gastric cancer, melanoma, microsatellite unstable (MSI) colorectal cancer or other MMR-deficient tumors, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, triple negative breast cancer, pancreatic ductal carcinoma, or transitional cell carcinoma of the genitourinary tract that have had disease progression after available therapies for advanced or metastatic disease that are known to confer clinical benefit, been intolerant to treatment, or refused standard treatment.
  • For Part 1b: Must have documented confirmed disease progression on a prior PD-1 pathway targeted agent or must be PD-1 pathway-targeted treatment naïve.
  • For Part 2
  • For subjects with SCLC:
  • Subjects with histologically or cytologically confirmed advanced or metastatic SCLC. Must not have had previous treatment with antibodies that modulate T-cell function or checkpoint pathways. Must have disease progression on or after platinum-based chemotherapy or must be intolerant to or refuse standard treatment. Must not have received more than 2 lines of prior therapy.
  • For subjects with NSCLC:
  • Subjects with a histologically or cytologically confirmed diagnosis of Stage IIIB, Stage IV, or recurrent NSCLC. Have not received more than 1 prior systemic therapy for metastatic NSCLC. No prior therapy with checkpoint inhibitors (anti-PD-1/PD-L1 or anti-CTLA-4). Have confirmation that EGFR or ALK-directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR mutations AND ALK gene rearrangements treatable with a tyrosine kinase inhibitor (TKI) OR presence of a KRAS mutation). If participant's tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK translocation will not be required as this is not part of current diagnostic guidelines. Have measurable disease based on RECIST 1.1.
  • For subjects with UC:
  • Subjects with a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra. Have had 1 prior treatment of systemic chemotherapy containing a platinum agent or is considered ineligible to receive cisplatin-based combination therapy. No prior therapy with checkpoint inhibitors (anti-PD-1/PD-L1 or anti-CTLA-4). Have measurable disease based on RECIST 1.1.

Who cannot join

  • Laboratory parameters not within the protocol-defined range.
  • Receipt of anticancer medications or investigational drugs within a defined interval before the first administration of study drug.
  • Received an immune-suppressive based treatment for any reason within 14 days prior to the first dose of study treatment.
  • Has not recovered from toxic effect of prior therapy to < Grade 1.
  • Active or inactive autoimmune process.
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • Active infection requiring systemic therapy.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Emory University, Winship Cancer Institute

    Atlanta, Georgia, 30322

  • The Center for Cancer and Blood Disorders (RCCA MD LLC-Maryland Vidision)

    Bethesda, Maryland, 20817

  • Beth Israel Medical Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer institute

    Boston, Massachusetts, 02215

  • Karmanos Cancer Center

    Detroit, Michigan, 48201

  • Henry Ford Hospital System

    Detroit, Michigan, 48202

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • St. Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • University of Kentucky, Markey Cancer Center

    Lexington, Kentucky, 40536

  • NYU Laura & Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • UPMC CancerCenters, Hilman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Hematology-Oncology Associates of Treasure Coast

    Port Saint Lucie, Florida, 37952

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • University of California San Francisco Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94143

  • John Wayne Cancer Institute at Providence Saint John's Health Center

    Santa Monica, California, 90404

  • HOPE Cancer Center of East Texas

    Tyler, Texas, 75701

  • Georgetown University Medical Center Lombardi CCC

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of Pembrolizumab + INCB Combinations in Advanced Solid Tumors

This is an open-label, multicenter, Phase 1b platform study in subjects with advanced or metastatic solid tumors (Part 1a) and subjects with selected solid tumors (Part 1b and Part 2). Two treatment groups (Group A and Group B) will be evaluated

Part 1a utilizes a 3+3 design to evaluate pembrolizumab and INCB combinations in advanced solid tumors. Group A will evaluate a JAK inhibitor with JAK1 selectivity itacitinib (INCB039110) in combination with pembrolizumab (MK-3475) and Group B will evaluate a PI3K-delta inhibitor (INCB050465) in combination with pembrolizumab to determine the maximum tolerated dose (MTD) or PAD and recommend a dose for the Part 1b safety expansion with each combination.

Read more

Once the recommended dose has been identified in Part 1a, subjects with select solid tumor types will be enrolled into safety expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b) for each combination.

Part 2 utilizes a Simon 2-Stage design to evaluate INCB050465 in combination with pembrolizumab in patients with small cell lung cancer (SCLC) and a 1 stage design to evaluate the combination in patients with non-small cell lung cancer (NSCLC) and urothelial cancer (UC).

Read the detailed description

This is an open-label, Phase 1b, 3 Part (Part 1a, Part 1b, and Part 2), multi-center study.

Part 1a utilizes a 3+3 design to evaluate pembrolizumab and INCB combinations in advanced solid tumors. Group A will evaluate a JAK inhibitor with JAK1 selectivity itacitinib (INCB039110) in combination with pembrolizumab (MK-3475) and Group B will evaluate a PI3K-delta inhibitor (INCB050465) in combination with pembrolizumab to determine the maximum tolerated dose (MTD) or PAD and recommend a dose for the Part 1b safety expansion with each combination.

Once the recommended dose has been identified in Part 1a, subjects with endometrial cancer, gastric cancer, melanoma, microsatellite unstable (MSI) colorectal cancer or other MMR-deficient tumors, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, triple negative breast cancer, pancreatic ductal carcinoma, or transitional cell carcinoma of the genitourinary tract will be enrolled into safety expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b) for each combination.

Part 2 utilizes a Simon 2-Stage design to evaluate INCB050465 in combination with pembrolizumab in patients with small cell lung cancer (SCLC) and a 1 stage design to evaluate the combination in patients with non-small cell lung cancer (NSCLC) and urothelial cancer (UC).

Being tested
Pembrolizumab, itacitinib, INCB050465
Keywords
Advanced
Medical subject headings
Colorectal Neoplasms, Endometrial Neoplasms, Melanoma, Head and Neck Neoplasms, Lung Neoplasms, Breast Neoplasms, Pancreatic Neoplasms, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Pembrolizumab 200 mg IV Q3W.

  • itacitinibDrug

    Also called INCB039110

    Itacitinib tablets administered orally once daily.

  • INCB050465Drug

    INCB050465 tablets administered orally once daily.

Study groups in NCT02646748
Study groupRoleWhat they receive
pembrolizumab + itacitinibExperimentalPart 1a Group A will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. Part 1b Group A-1 and Group A-2 will evaluate the MTD or PAD of itacitinib in combination with pembrolizumab in subjects with select solid tumors.
Receives: Drug: Pembrolizumab; Drug: itacitinib
pembrolizumab + INCB050465ExperimentalPart 1a Group B will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. Part 1b Group B-1 and Group B-2 will evaluate the MTD or PAD of INCB050465 in combination with pembrolizumab in subjects with select solid tumors. Part 2 will evaluate the combination of INCB050465 in combination with pembrolizumab in subjects with small cell lung cancer, non-small lung cancer and urothelial cancer.
Receives: Drug: Pembrolizumab; Drug: INCB050465

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Evaluation of safety and tolerability as measured by the frequency, duration, and severity of adverse events

    Measured: Duration of study treatment and up to 120 days after the last dose of study drug

Secondary outcomes (2)

  1. Part 1 and 2: Objective Response Rate (ORR) as determined by radiographic disease assessments per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) v1.1 criteria

    Measured: Every 9 weeks for the first year on study

  2. Part 1 and 2: Change in the number of Tumor Infiltrating Lymphocytes(TILs) and the ratio of CD8+ lymphocytes to FOXP3+ cells infiltrating tumor post-treatment versus pretreatment by IHC

    Measured: Up to 5 weeks on study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2016 (estimated)
  2. Study start25 Jan 2016
  3. Primary completion7 Nov 2019
  4. Study completion20 Nov 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
159 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02646748
Sponsor's protocol ID
39110-107
Status last verified
Mar 2022
First submitted
4 Jan 2016
Last updated
31 Mar 2022
Results posted
No
Data monitoring committee
No

Publications

  • Munster P, Iannotti N, Cho DC, Kirkwood JM, Villaruz LC, Gibney GT, Hodi FS, Mettu NB, Jones M, Bowman J, Smith M, Lakshminarayanan M, O'Day S. Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study. Cancer Res Commun. 2023 Dec 19;3(12):2572-2584. doi: 10.1158/2767-9764.CRC-22-0461.

    PubMed 38115208

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab, itacitinib and INCB050465 in people with Colorectal Cancer (CRC) and Endometrial Cancer, run by Incyte Corporation at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Evaluation of safety and tolerability as measured by the frequency, duration, and severity of adverse events (time frame: Duration of study treatment and up to 120 days after the last dose of study drug). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02646748, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2022.

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