Phase 1 Study of CK-301 (Cosibelimab) as a Single Agent in Subjects With Advanced Cancers

Sponsor

Checkpoint Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03212404

Collaborator

Novotech (Australia) Pty Limited (Industry)

500

Enrollment

Locations

Arm

74.3

Anticipated Duration (Months)

10.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: CK-301 (cosibelimab)	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 20, 2017

Actual Primary Completion Date :

Nov 18, 2021

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CK-301 (cosibelimab) Part 1 - Dose Escalation; Part 2 - Dose Expansion	Drug: CK-301 (cosibelimab) CK-301 will be administered in periods of 28-day cycles.

Arm

Intervention/Treatment

Experimental: CK-301 (cosibelimab)

Part 1 - Dose Escalation; Part 2 - Dose Expansion

Drug: CK-301 (cosibelimab)

CK-301 will be administered in periods of 28-day cycles.

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity [Up to 4 weeks]
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) [Screening through 4 weeks after study completion, an average of 6 months]
Confirmed Objective Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) [Part 2 Only: Average of 6 months]

Secondary Outcome Measures

Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) [Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months]
Duration of Response (DoR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) [Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months]
Objective response rate and duration of response (DOR) based on Modified RECIST 1.1 for immune based therapeutics [Part 2 Only: Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months]
Overall Survival (OS) [Part 2 Only: Every 8 weeks for first 32 weeks, then 12 weeks through study completion, an average of 6 months]
Pharmacokinetic parameter: AUC (0-t) of CK-301 [Baseline up to 12 weeks after study completion, an average of 6 months]
Pharmacokinetic parameter: AUC (0-infinity) of CK-301 [Baseline up to 12 weeks after study completion, an average of 6 months]
Pharmacokinetic parameter: Cmax of CK-301 [Baseline up to 12 weeks after study completion, an average of 6 months]
Pharmacokinetic parameter: Tmax of CK-301 [Baseline up to 12 weeks after study completion, an average of 6 months]
Pharmacokinetic parameter: T(1/2) of CK-301 [Baseline up to 12 weeks after study completion, an average of 6 months]
Number of subjects with anti-CK-301 antibodies [Baseline up to 12 weeks after study completion, an average of 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Wollongong	New South Wales	Australia	2500
2	Research Site	Benowa	Queensland	Australia	4217
3	Research Site	Buderim	Queensland	Australia	4556
4	Research Site	Greenslopes	Queensland	Australia	4120
5	Research Site	South Brisbane	Queensland	Australia	4101
6	Research Site	Woolloongabba	Queensland	Australia	4102
7	Research Site	Box Hill	Victoria	Australia	3128
8	Research Site	Malvern	Victoria	Australia	3144
9	Research Site	Besançon		France	25030
10	Research Site	Bordeaux		France	33075
11	Research Site	Grenoble		France	38700
12	Research Site	Lyon		France	69495
13	Research Site	Nice		France
14	Research Site	Christchurch		New Zealand	8140
15	Research Site	Kraków		Poland	31-826
16	Research Site	Lublin		Poland	20064
17	Research Site	Poznań		Poland	60693
18	Research Site	Warsaw		Poland	02-781
19	Research Site	Łódź		Poland	90302
20	Research Site	Chelyabinsk		Russian Federation	454087
21	Research Site	Kazan		Russian Federation	420029
22	Research Site	Murmansk		Russian Federation	183047
23	Research Site	Novosibirsk		Russian Federation	630108
24	Research Site	Omsk		Russian Federation	644013
25	Research Site	Saint Petersburg		Russian Federation	197022
26	Research Site	Saint Petersburg		Russian Federation	197758
27	Research Site	Tyumen		Russian Federation	625041
28	Research Site	Volgograd		Russian Federation	400138
29	Research Site	Cape Town		South Africa	7700
30	Research Site	George		South Africa	6529
31	Research Site	Port Elizabeth		South Africa
32	Research Site	Pretoria		South Africa	0081
33	Research Site	Soweto		South Africa	2013
34	Research Site	Barcelona		Spain
35	Research Site	La Laguna		Spain	38320
36	Research Site	Madrid		Spain
37	Research Site	Málaga		Spain
38	Research Site	Pamplona		Spain	31008
39	Research Site	Sevilla		Spain
40	Research Site	Valencia		Spain
41	Research Site	Hat Yai	Songkhla	Thailand	90110
42	Research Site	Bangkok		Thailand	10210
43	Research Site	Bangkok		Thailand	10330
44	Research Site	Chiang Mai		Thailand	50200
45	Research Site	Khon Kaen		Thailand	40002
46	Research Site	Chernivtsi		Ukraine	58013
47	Research Site	Kharkiv		Ukraine	61103
48	Research Site	Sumy		Ukraine	40022