Clinical trial NCT03212404: Phase 1 Study of CK-301 (Cosibelimab) as a Single Agent in Subjects With Advanced Cancers
Official title: A Phase 1, Open-label, Multicenter, Dose-escalation Study of CK-301 Administered Intravenously as a Single Agent to Subjects With Advanced Cancers
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Small Cell
Malignant Mesothelioma, Advanced
Head and Neck Cancer
Melanoma
Merkel Cell Carcinoma
Renal Cell Carcinoma
Urothelial Carcinoma
Classical Hodgkin Lymphoma
Cutaneous Squamous Cell Carcinoma
Non Hodgkin Lymphoma
Endometrial Cancer
Keywords: Cancer
PD-L1
PDL1
PD-1
PD1
Solid tumors
Anti PD-L1
Non-small cell lung cancer, NSCLC
CK-301
CSCC
Skin cancer
Lead sponsor: Checkpoint Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2017-07-11
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: CK-301 (cosibelimab) is a fully human monoclonal antibody of IgG1 subtype that directly binds to Programmed Death-Ligand 1 (PD-L1) and blocks its interactions with the Programmed Death-1 (PD-1) and B7.1 receptors. The primary objectives of this study are to assess the safety, tolerability and efficacy of CK-301 when administered intravenously as a single agent to subjects with selected recurrent or metastatic cancers.

Detailed description: This is a first-in-human, Phase 1, open-label, multicenter, dose-escalation study of CK-301 (cosibelimab), a fully human monoclonal IgG1 antibody targeting PD-L1. The study will consist of 3 periods: Screening (up to 28 days), Treatment (28-day cycles), and Follow-up (up to 6 months of visits with survival follow-up for select cohorts). Following the dose escalation portion of the study, additional evaluable subjects may be included in order to further characterize safety and efficacy at selected doses and/or in specific patient sub-groups.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent.
* Male or female subjects aged greater than or equal to 18 years.
* For NSCLC: Histologically or cytologically confirmed diagnosis of unresectable recurrent or metastatic non-small cell lung cancer.
* For CRC: Histologically confirmed diagnosis of recurrent or metastatic colorectal cancer assessed as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
* For EC: Histologically or cytologically confirmed advanced, recurrent or metastatic endometrial carcinoma.
* For cSCC: Histologically confirmed diagnosis of unresectable or metastatic cutaneous squamous cell carcinoma not amenable to local therapy.
* For SCLC: Histologically or cytologically confirmed diagnosis of unresectable small cell lung cancer.
* For MPM: Histologically or cytologically confirmed diagnosis of unresectable malignant pleural or peritoneal mesothelioma.
* For HNSCC: Histologically or cytologically confirmed diagnosis of recurrent or metastatic HNSCC (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
* For MEL: Histologically confirmed diagnosis of unresectable Stage III or metastatic melanoma not amenable to local therapy (excluding uveal or ocular melanoma).
* For MCC: Histologically confirmed diagnosis of metastatic Merkel cell carcinoma not amenable to local therapy.
* For RCC: Histologically confirmed diagnosis of renal cell carcinoma (with clear cell component) with advanced or metastatic disease that is not amenable to cure by surgery or other means.
* For UC: Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra) not amenable to cure by surgery or other means.
* For HL: Histologically confirmed primary diagnosis of classical Hodgkin's lymphoma.
* For B-cell NHL: Histologically confirmed diagnosis of non-Hodgkin lymphoma.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
* Must have at least one measurable lesion based on RECIST 1.1.
* Have provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated.
* Adequate hematological, hepatic and renal function as defined in the protocol.
* Effective contraception for both male and female subjects if the risk of conception exists.
* Other protocol defined inclusion criteria could apply.

Exclusion Criteria:

* Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
* Concurrent treatment with a non-permitted drug.
* History of severe hypersensitivity reactions to other monoclonal antibodies.
* Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, or localized prostate cancer.
* Chemotherapy, radioactive, biological cancer therapy, or tyrosine kinase inhibitor (TKI) therapy, within four weeks prior to the first dose of study drug, or who has not recovered to NCI CTCAE Grade 1 or better from the AEs due to cancer therapeutics administered more than four weeks earlier.
* Significant acute or chronic infections as defined in the protocol.
* Active or history of interstitial lung disease (ILD), or has had a history of pneumonitis that has required oral or IV steroids.
* Active or suspected autoimmune disease or a documented history of autoimmune disease.
* Known current drug or alcohol abuse.
* Underlying medical conditions that will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events.
* Use of other investigational therapy within 28 days before study drug administration.
* Pregnant or breastfeeding.
* Uncontrolled or significant cardiovascular disease.
* Psychiatric illness or social situation that would preclude study compliance.
* Receipt of live, attenuated vaccine within 28 days prior to the first dose of study drug.

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: Up to 4 weeks
measure: Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 (or most current version)
timeFrame: Screening through 4 weeks after study completion, an average of 6 months
measure: Confirmed Objective Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
timeFrame: Part 2 Only: Average of 6 months
Secondary outcomes:
measure: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
timeFrame: Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months
measure: Duration of Response (DoR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)
timeFrame: Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months
measure: Objective response rate and duration of response (DOR) based on Modified RECIST 1.1 for immune based therapeutics
timeFrame: Part 2 Only: Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months
measure: Overall Survival (OS)
timeFrame: Part 2 Only: Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months
measure: Pharmacokinetic parameter: AUC (0-t) of CK-301
timeFrame: Baseline up to 12 weeks after study completion, an average of 6 months
measure: Pharmacokinetic parameter: AUC (0-infinity) of CK-301
timeFrame: Baseline up to 12 weeks after study completion, an average of 6 months
measure: Pharmacokinetic parameter: Cmax of CK-301
timeFrame: Baseline up to 12 weeks after study completion, an average of 6 months
measure: Pharmacokinetic parameter: Tmax of CK-301
timeFrame: Baseline up to 12 weeks after study completion, an average of 6 months
measure: Pharmacokinetic parameter: T(1/2) of CK-301
timeFrame: Baseline up to 12 weeks after study completion, an average of 6 months
measure: Number of subjects with anti-CK-301 antibodies
timeFrame: Baseline up to 12 weeks after study completion, an average of 6 months
Other outcomes:
Locations:
city: Wollongong
country: Australia
facility: Research Site
state: New South Wales
city: Benowa
country: Australia
facility: Research Site
state: Queensland
city: Buderim
country: Australia
facility: Research Site
state: Queensland
city: Greenslopes
country: Australia
facility: Research Site
state: Queensland
city: South Brisbane
country: Australia
facility: Research Site
state: Queensland
city: Woolloongabba
country: Australia
facility: Research Site
state: Queensland
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Malvern
country: Australia
facility: Research Site
state: Victoria
city: Besançon
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Grenoble
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Murmansk
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Tyumen
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: George
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Soweto
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: La Laguna
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
state: Songkhla
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Chernivtsi
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
Study officials:
References: