Kidney Cancer Clinical Trial

Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors

Summary

This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of SRF388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.

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Full Description

This is a Phase 1/1b, open-label, first-in-human (FIH), dose-escalation and expansion study of CHS-388, a monoclonal antibody targeting IL-27, as a monotherapy and in combination in patients with solid tumors that will be conducted in 4 parts:

Part A: CHS-388 monotherapy dose-escalation portion of the study will evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of CHS-388 as monotherapy in patients with advanced solid tumors.
Part B: CHS-388 monotherapy expansion cohorts will evaluate the safety, efficacy, tolerability, PK, and pharmacodynamics of CHS-388 monotherapy in patients with advanced or metastatic ccRCC, advanced or metastatic HCC, and advanced or metastatic NSCLC in indication specific cohorts.
Part C will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with pembrolizumab in patients with advanced RCC,HCC, or NSCLC.
Part D will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with toripalimab in patients with advanced NSCLC.

View Eligibility Criteria

Eligibility Criteria

Part A and Part B Abbreviated Inclusion Criteria:

≥ 18 years of age
Locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy, and for whom no available therapies are appropriate (based on investigator judgment)
Patients in Part B with advanced or metastatic ccRCC, HCC, or NSCLC must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Patients with HCC in Part B must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization [TACE]) or Stage C
For patients in Part B with ccRCC, demonstrated progressive disease (PD) during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with regimen(s) that have included a vascular endothelial growth factor (VEGF)-targeted agent and an immune checkpoint inhibitor. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
For patients in Part B with HCC, demonstrated PD during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with a VEGF-targeted agent. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
For Part B patients in the tumor biopsy subsets only, must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol
Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN)
Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤ 2 x ULN for patients with HCC or patients with known liver metastases)
Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) < 2.5 x ULN (< 5 x ULN if liver metastasis or for patients with HCC)
For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L. For patients with HCC, platelet count ≥ 75 x 109/L without transfusion
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Patients with NSCLC must have histologically confirmed locally advanced and/or metastatic Stage IV NSCLC
Patients with NSCLC must have demonstrated progressive disease during or after the most recent treatment regimen

Part C Abbreviated Inclusion Criteria:

≥ 18 years of age
Advanced RCC of any histology or advanced HCC previously treated with at least one systemic anticancer therapy OR histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC) Stage B (not eligible for transcatheter arterial chemoembolization) or Stage C
At least 1 measurable lesion per RECIST 1.1
Patients with HCC must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
ECOG performance status of 0-1
ANC ≥1500/µL (1.5 x 109/L)
Platelets ≥100 000/µL (≥ 100 x 109/L)
Hemoglobin for participants with RCC: ≥9.0 g/dL; for participants with HCC: ≥8.5 g/dL
Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
For patients with HCC, Child-Pugh Class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 120 days after the last dose of pembrolizumab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.

Part C Abbreviated Inclusion Criteria Specific to Patients with RCC or HCC from Part A or Part B:

Progressed on CHS-388 by RECIST 1.1
Did not experience prior Grade ≥ 3 toxicity related to CHS-388
Willingness to undergo pretreatment core or excisional biopsy if deemed safe and tumor is accessible, in the opinion of the Investigator
Has received no systemic anticancer therapies between CHS-388 doses

Part C Abbreviated Inclusion Criteria specific to NSCLC Patients:

No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination

Part A and Part B Abbreviated Exclusion Criteria:

Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
For patients with HCC, known fibrolamellar or mixed hepatocellular cholangiocarcinoma
History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
Major surgery within 4 weeks prior to Screening
Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study

Part C Abbreviated Exclusion Criteria:

Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
No prior systemic therapy for unresectable or metastatic disease
Received > 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
For patients with HCC, moderate or severe ascites
For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
Prior autologous stem cell transplant ≤ 3 months before the first dose
Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
Has had an allogenic tissue/solid organ transplant
Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study

Part D Abbreviated Inclusion Criteria

≥ 18 years of age
Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
At least 1 measurable lesion per RECIST 1.1
ECOG performance status of 0-1
ANC ≥1500/µL (1.5 x 109/L)
Platelets ≥100 000/µL (≥ 100 x 109/L)
Hemoglobin for participants with RCC: ≥9.0 g/dL
Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 180 days after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.

Part D Abbreviated Exclusion Criteria:

Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
No prior systemic therapy for unresectable or metastatic disease
Received > 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a ≥ Grade 3 irAE.

because of contrast allergy or other contraindication

History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
Prior autologous stem cell transplant ≤ 3 months before the first dose
Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
Has had an allogenic tissue/solid organ transplant
Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study

Study is for people with:

Kidney Cancer

Phase:

Phase 1

Estimated Enrollment:

260

Study ID:

NCT04374877

Recruitment Status:

Recruiting

Sponsor:

Coherus Biosciences, Inc.

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There are 21 Locations for this study

See Locations Near You

City of Hope
Duarte California, 91010, United States More Info
Daneng Li
Contact
626-471-9200
Daneng Li, MD
Principal Investigator
University of Southern California (USC) - Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States More Info
Xiomara Menendez, RN
Contact
323-409-4368
[email protected]
Lisa Harton, MS
Contact
(323) 865-0454
[email protected]
Anthony El-Khoueiry, MD
Principal Investigator
UCSF Medical Center - Helen Diller Family Comprehensive Cancer Center
San Francisco California, 94143, United States More Info
Ria Conti
Contact
415-514-2259
[email protected]
Arpita Desai, MD
Principal Investigator
University of Miami Leonard M. Miller School of Medicine (UMMSM)
Miami Florida, 33136, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Karly Griffin
Contact
617-632-6287
[email protected]
Charlene Mantia, MD
Principal Investigator
University of Michigan Health System (UMHS)
Ann Arbor Michigan, 48109, United States More Info
Breanna Bladowski
Contact
734-936-7813
[email protected]
Ulka Vaishampayan, MD
Principal Investigator
Washington University School of Medicine - St. Louis
Saint Louis Missouri, 63110, United States More Info
Allie Gordon
Contact
314-747-5543
[email protected]
Katlyn Kraft
Contact
314-747-5440
[email protected]
Daniel Morgensztern, MD
Principal Investigator
Roswell Park
Buffalo New York, 14263, United States More Info
Rushka Kallicharan Smith
Contact
[email protected]
Saby George, MD
Principal Investigator
Icahn School of Medicine at Mount Sinai (ISMMS) - The Mount Sinai Hospital (MSH)
New York New York, 10029, United States More Info
Natalie Lucas
Contact
929-489-5016
[email protected]
Thomas Marron, MD
Principal Investigator
Cleveland Clinic
Cleveland Ohio, 44195, United States More Info
Moshe Ornstein, MD
Principal Investigator
University of Oklahoma Health Sciences Center (OUHSC) - Stephenson Cancer Center
Oklahoma City Oklahoma, 73104, United States More Info
Abdul Naqash, MD
Principal Investigator
University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center (University of Pittsburgh Cancer Institute (UPCI))
Pittsburgh Pennsylvania, 15232, United States More Info
Annalisa Brenneman
Contact
412-623-2293
[email protected]
Leonard Appleman, MD
Principal Investigator
Vanderbilt University Medical Center (VUMC)
Nashville Tennessee, 37232, United States More Info
VICC Recruitment and Eligibility Office
Contact
800-811-8480
Brian Rini, MD
Principal Investigator
University of Texas Southwestern Medical Center
Dallas Texas, 75390, United States More Info
Amy Rowell
Contact
214-648-7001
[email protected]
Hans Hammers, MD
Principal Investigator
The University of Texas - MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Serdar A. Gurses, PhD
Contact
713-563-9710
[email protected]
Yanyan Tian, PhD
Contact
713-792-7274
[email protected]
Aung Naing, MD
Principal Investigator
South Texas Accelerated Research Therapeutics
San Antonio Texas, 78229, United States More Info
Angela Galindo
Contact
210-593-5202
[email protected]
Amita Patnaik, MD
Principal Investigator
Seoul National University Hospital
Seoul , 03080, Korea, Republic of More Info
HyunJoo Ryu
Contact
+82-2-6072-5175
[email protected]
Tae-Yong Kim, MD
Principal Investigator
Severance Hospital
Seoul , 03722, Korea, Republic of More Info
Sun Young Rha, MD
Principal Investigator
Asan Medical Center
Seoul , 05505, Korea, Republic of More Info
SeoJin Moon
Contact
82-2-3010-8351
[email protected]
Yoon-Koo Kang, MD
Principal Investigator
National University Hospital
Singapore , 11922, Singapore More Info
Cheng Ean Chee, MD
Contact
(65) 6779 5555
[email protected]
Shi Jian Eric Foo
Contact
(65)92478406
[email protected]
Cheng Ean Cheng Ean, MD
Principal Investigator
National Cancer Center Singapore (NCCS)
Singapore , 16961, Singapore

How clear is this clinincal trial information?

Study is for people with:

Kidney Cancer

Phase:

Phase 1

Estimated Enrollment:

260

Study ID:

NCT04374877

Recruitment Status:

Recruiting

Sponsor:


Coherus Biosciences, Inc.

How clear is this clinincal trial information?

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