INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

Sponsor
Incyte Corporation (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04580485
Collaborator
(none)
230
28
2
38.2
8.2
0.2

Study Details

Study Description

Brief Summary

This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC)

Study Design

Study Type:
Interventional
Anticipated Enrollment :
230 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
Open Label
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors
Actual Study Start Date :
Feb 3, 2021
Anticipated Primary Completion Date :
Apr 10, 2024
Anticipated Study Completion Date :
Apr 10, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment Group A (TGA) - INCB106385

In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.

Drug: INCB106385
INCB106385 will be administered orally QD

Experimental: Treatment Group B (TGB) - INCB106385+INCMGA00012

In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.

Drug: INCB106385
INCB106385 will be administered orally QD

Drug: INCMGA00012
INCMGA0012 will be administered IV once every 4 weeks (Q4W)

Outcome Measures

Primary Outcome Measures

  1. Number of treatment-emergent adverse events (TEAE) [Up to Approximately 28 months]

    Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after last dose of study drug.

Secondary Outcome Measures

  1. Cmax of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]

    Maximum observed plasma concentration.

  2. Tmax of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]

    Time to maximum plasma concentration

  3. Cmin of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]

    Minimum observed plasma concentration over the dose interval

  4. AUC of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]

    Area under the plasma concentration-time curve

  5. CL/F of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]

    Apparent oral dose clearance

  6. Objective Response Rate (ORR) [Up to approximately 24 months]

    Defined as the percentage of participants with a best overall response of CR or PR, as determined by investigator radiographic disease assessment according to RECIST v1.1.

  7. Disease Control Rate [Up to approximately 24 months]

    Defined as the percentage of participants with a best overall response of CR, PR, or SD, as determined by investigator radiographic disease assessment according to RECIST v1.1.

  8. Duration Of Response (DOR) [Up to approximately 24 months]

    Defined as the time from the earliest date of CR or PR until the earliest date of disease progression, as determined by investigator radiographic disease assessment according to RECIST v1.1, or death due to any cause if occurring sooner than progression.

  9. Change in tumoral gene expression [Predose and Week 5-6]

    Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline

  10. Change in immune cell activation in tumors [Predose and Week 5-6]

    Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Ability to comprehend and willingness to sign an ICF.

  • Willing and able to conform to and comply with all Protocol requirements.

  • Histologically or cytologically confirmed advanced/metastatic SCCHN, NSCLC, ovarian cancer, TNBC, CRPC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC) that progressed after treatment with available therapies (including anti PD-(L)1 therapy (if applicable).

  • Willingness to undergo pre- and on-treatment tumor biopsy.

  • Have CD8 T-cell-positive tumors.

  • Presence of measurable disease according to RECIST v1.1.

  • ECOG performance status 0 to 1.

  • Life expectancy > 12 weeks.

  • Willingness to avoid pregnancy or fathering children based.

  • Acceptable laboratory parameters

Exclusion Criteria:
  • Clinically significant cardiac disease.

  • Known or active CNS metastases and/or carcinomatous meningitis.

  • Active or inactive autoimmune disease or syndrome that required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease..

  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses

10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.

  • Known additional malignancy that is progressing or requires active treatment,or history of other malignancy within 2 years of the first dose of study treatment.

  • Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.

  • Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.

  • Immune-related toxicity during prior immune therapy for which permanent discontinuation of therapy is recommended, or any immune-related toxicity requiring intensive or prolonged immunosuppression to manage.

  • Any prior chemotherapy, biological therapy, or targeted therapy to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.

  • Any prior radiation therapy within 28 days before the first dose of study treatment.

  • Undergoing treatment with another investigational medication or having been treated with an investigational medication within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.

  • Concomitant treatment with strong CYP3A4 inhibitors or inducers.

  • Receipt of a live vaccine within 30 days of the first dose of study treatment.

  • Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of the first dose of study treatment.

  • Evidence of HBV or HCV infection or risk of reactivation.

  • Known history of HIV (HIV 1/2 antibodies).

  • History of organ transplant, including allogeneic stem-cell transplantation.

  • Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.

  • Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.

  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.

  • Any condition that would, in the investigator's judgment, interfere with full participation in the study,pose a significant risk to the participant; or interfere with interpretation of study data

Contacts and Locations

Locations

Site City State Country Postal Code
1 Cedars-Sinai Medical Center West Hollywood California United States 90048
2 University of Maryland - Greenebaum Cancer Center Baltimore Maryland United States 21201
3 Dana Farber Cancer Institute Boston Massachusetts United States 02215
4 Roswell Park Cancer Institute Buffalo New York United States 14263
5 Columbia University Medical Center New York New York United States 10032
6 University of Pittsburgh Pittsburgh Pennsylvania United States 15232
7 Md Anderson Cancer Center Houston Texas United States 77030
8 South Texas Accelerated Research Therapeutics San Antonio Texas United States 78229
9 Cliniques Universitaires Ucl Saint-Luc Brussels Belgium 01200
10 Universitaire Ziekenhuis Leuven - Gasthuisberg Leuven Belgium 03000
11 Institut Bergonie Bordeaux France 33000
12 Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole Toulouse France 31059
13 Institut Gustave Roussy Villejuif France 94800
14 A.O.U. Di Modena - Policlinico Modena Italy 41124
15 Istituto Nazionale Tumori Irccs Fondazione Pascale Naples Italy 80131
16 Irccs Istituto Clinico Humanitas Rozzano Italy 20089
17 Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) Verona Italy 37134
18 Hospital General Universitario Vall D Hebron Barcelona Spain 08035
19 Fundacion Jimenez Diaz University Hospital Madrid Spain 28040
20 Hospital Universitario 12 de Octubre Madrid Spain 28041
21 Centro Integral Oncologico Clara Campal (Ciocc) Madrid Spain 28050
22 Clinica Universidad de Navarra (Cun) Pamplona Spain 31008
23 Cambridge University Hospitals Nhs Foundation Trust Cambridge United Kingdom CB2 0QQ
24 University of Glasgow Glasgow United Kingdom G12 0YN
25 Guys and St Thomas Nhs Foundation Trust London United Kingdom SE1 9RT
26 Imperial College Healthcare Nhs Trust - Hammersmith Hospital London United Kingdom W12 0HS
27 The Christie Nhs Foundation Trust Uk Manchester United Kingdom M20 4BV
28 Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust Newcastle Upon Tyne United Kingdom NE7 7DN

Sponsors and Collaborators

  • Incyte Corporation

Investigators

  • Study Director: Ilona Rybicka, M.D, Incyte Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT04580485
Other Study ID Numbers:
  • INCB 106385-102
First Posted:
Oct 8, 2020
Last Update Posted:
Jun 29, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Incyte Corporation
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 29, 2022