INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors
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
Arms and Interventions
Arm | Intervention/Treatment |
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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
- 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
- Cmax of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]
Maximum observed plasma concentration.
- Tmax of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]
Time to maximum plasma concentration
- Cmin of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]
Minimum observed plasma concentration over the dose interval
- AUC of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]
Area under the plasma concentration-time curve
- CL/F of INCB106385 as a single agent or in combination with INCMGA00012 [Up to 6 months]
Apparent oral dose clearance
- 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.
- 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.
- 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.
- 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
- 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
Inclusion Criteria:
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Ability to comprehend and willingness to sign an ICF.
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Willing and able to conform to and comply with all Protocol requirements.
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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).
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Willingness to undergo pre- and on-treatment tumor biopsy.
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Have CD8 T-cell-positive tumors.
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Presence of measurable disease according to RECIST v1.1.
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ECOG performance status 0 to 1.
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Life expectancy > 12 weeks.
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Willingness to avoid pregnancy or fathering children based.
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Acceptable laboratory parameters
Exclusion Criteria:
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Clinically significant cardiac disease.
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Known or active CNS metastases and/or carcinomatous meningitis.
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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..
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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.
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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.
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Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.
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Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
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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.
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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.
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Any prior radiation therapy within 28 days before the first dose of study treatment.
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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.
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Concomitant treatment with strong CYP3A4 inhibitors or inducers.
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Receipt of a live vaccine within 30 days of the first dose of study treatment.
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Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of the first dose of study treatment.
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Evidence of HBV or HCV infection or risk of reactivation.
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Known history of HIV (HIV 1/2 antibodies).
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History of organ transplant, including allogeneic stem-cell transplantation.
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Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.
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Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
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Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
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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 | |
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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.- INCB 106385-102