Conditions: Metastatic Non-squamous Non Small Cell Lung Cancer
Keywords: Metastatic non-small cell lung cancer nonsquamous PD-L1 PD-1 PDL1 PD1 Lung neoplasms Cosibelimab Non-squamous NSCLC Carcinoma, non-small cell lung Antineoplastic agents CK-301 Anti-PD-L1
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 25
Healthy volunteers: no

Brief summary:
This is an efficacy and safety study of cosibelimab (CK-301) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone in participants with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned in a 2:1 ratio to receive cosibelimab combined with pemetrexed/platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed/platinum (Investigators choice of cisplatin or carboplatin).

The primary hypothesis is that cosibelimab in combination with pemetrexed/platinum chemotherapy prolongs Overall Survival (OS) compared to pemetrexed/platinum chemotherapy alone.

Detailed description:
CK-301-301 is a Phase 3, open-label, multicenter, randomized, active-controlled study of the safety and efficacy of IV administered cosibelimab 1200 mg Q3W in combination with platinum/pemetrexed chemotherapy versus chemotherapy alone in subjects with NSCLC who have not previously received systemic therapy for advanced disease and in whom epidermal growth factor receptor-directed therapy or anaplastic lymphoma kinase-directed therapy was not indicated. Subjects were randomized 2:1 to receive cosibelimab 1200 mg in combination with pemetrexed and platinum therapy, or pemetrexed and platinum therapy alone. Subjects were stratified by smoking status (never versus former/current), cisplatin vs carboplatin, and PD-L1 status (Tumor Proportion Score \[TPS\] \< 1% vs 1-49% vs ≥ 50%) prior to randomization. Subjects with unevaluable PD-L1 status were included with the TPS \< 1% group.

Arms:
arm 1: Participants receive cosibelimab 1200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by cosibelimab 1200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression. arm 2: Participants receive pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pemetrexed 500 mg/m\^2 IV Q3W until progression.

Interventions: intervention 1: Cosibelimab intervention 2: Cisplatin intervention 3: Carboplatin intervention 4: Pemetrexed intervention 5: Folic acid 350-1000 μg intervention 6: Vitamin B12 1000 μg intervention 7: Dexamethasone 4mg
Intervention descriptions: intervention 1: IV infusion intervention 2: IV infusion intervention 3: IV infusion intervention 4: IV infusion intervention 5: Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed. intervention 6: Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration. intervention 7: For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Protocol document:
Prot_SAP_001.pdf: 
Clinical Trial Protocol Number: CK-301-301 
Protocol Version 1.0 
TITLE PAGE 
A Randomized, Open-Label, Phase 3 Study of Cosibelimab (CK-301) in 
Combination with Platinum+Pemetrexed Chemotherapy in Subjects with 
First-Line Metastatic Non-squamous Non-Small Cell Lung Cancer 
Protocol Number: 
CK-301-301 
EudraCT Number: 
N/A 
Trial Drug: 
Cosibelimab (CK-301) 
Sponsor: 
Checkpoint Therapeutics, Inc. 
2 Gansevoort Street, 9th floor 
New York, NY 10014, USA 
(212) 574-2830
Phase: 
Phase 3 
Version: 
Date Final: 
1.0 
12 January 2021 
CONFIDENTIAL 
The information contained in this document, especially any unpublished data, is the property of Checkpoint Therapeutics, 
Inc. (or under its control) and therefore is provided to you in confidence as an investigator, potential investigator, or 
consultant, for review by you, your staff, and an applicable Ethics Committee or Institutional Review Board. It is 
understood that this information will not be disclosed to others without written authorization from Checkpoint 
Therapeutics, Inc. except to the extent necessary to obtain informed consent from persons to whom the drug may be 
administered. 


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PROTOCOL SYNOPSIS 
Title of Trial: 
A Randomized, Open-Label, Phase 3 Study of Cosibelimab (CK-301) in Combination with 
Platinum+Pemetrexed Chemotherapy in Subjects with First-Line Metastatic Non-squamous 
Non-Small Cell Lung Cancer 
Protocol Number: 
CK-301-301 
Sponsor: 
Checkpoint Therapeutics, Inc. 
Phase of Trial: 
Phase 3 
Introduction: 
Cosibelimab (CK-301) 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. Normally, PD-L1 binds to PD-1 or B7.1 to 
stop an immune response and prevent autoimmunity/promote self-tolerance. Cancer cells are 
able to express PD-L1 and can use this to evade the body’s immune response. An 
anti-PD-L1 antibody, such as cosibelimab, could prevent PD-1/PD-L1 binding and 
reactivate the anti-tumor immune response.  
Clinical studies have shown that blockade of the PD-1/PD-L1 pathway by monoclonal 
antibodies can enhance the immune response and result in anti-tumor activity. PD-L1 is the 
primary PD-1 ligand that is up-regulated in solid tumors, where it can inhibit cytokine 
production and the cytolytic activity of PD-1+, tumor-infiltrating CD4+ and CD8+ T 
cells.1,2,3 These properties make PD-L1 a target for cancer immunotherapy. In addition, by 
retaining a native Fc-region, cosibelimab may also be capable of mediating 
antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells. 
In this trial, cosibelimab in combination with chemotherapy will be compared with 
chemotherapy alone in subjects with advanced or metastatic non-squamous, non-small cell 
lung cancer (NSCLC) who have not previously received systemic therapy. The primary 
objective of this trial is to evaluate the antitumor activity of cosibelimab in combination with 
chemotherapy compared with chemotherapy alone using Overall Survival (OS). 
Trial Type: 
Interventional. 
Type of Control: 
Active control, without placebo. 
Trial Blinding: 
Unblinded, open-label. 
Treatment Groups: 
There are 2 treatment arms: 
• 
Cosibelimab plus pemetrexed and carboplatin or cisplatin. 
• 
Pemetrexed and carboplatin or cisplatin. 
# of Subjects: 
Approximately 560 subjects are planned to be enrolled. 
Randomization 
Ratio: 
Randomized 2:1 to either receive cosibelimab combined with pemetrexed and platinum 
(investigator’s choice of cisplatin or carboplatin), or pemetrexed and platinum 
(investigator’s choice of cisplatin or carboplatin). 
Estimated 
Duration of Trial: 
The Sponsor estimates that the trial will require approximately 4 years from the time the first 
subject signs the informed consent until the last subject’s last study-related phone call or 
visit. 
Duration of 
Participation: 
Subjects will participate in the trial from the time the subject signs the Informed Consent 
Form (ICF) through the final contact. After a screening phase of up to 28 days, eligible 
subjects will receive assigned treatment on Day 1 of each 3-week (Q3W) dosing cycle.  
Subjects randomized to the cosibelimab arm will continue treatment until the first 
occurrence of either: 1) confirmed and worsening radiographic progressive disease (PD), 


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defined as an additional 10% or greater increase in tumor burden volume from time of initial 
radiographic disease progression (including all target lesions and new measurable lesions); 
2) clinical deterioration suggesting that no further benefit from treatment is likely; 3) 
unacceptable adverse experiences; or 4) meets other criteria for discontinuation as outlined 
in Section 3.13 (Subject withdrawal/Discontinuation Criteria). Subjects with confirmed and 
worsening PD are permitted to continue cosibelimab treatment if there is clinical stability as 
assessed by the Investigator, as outlined in Section 3.13.  
Subjects randomized to the chemotherapy arm will continue treatment until the first 
occurrence of either: 1) confirmed radiographic PD; 2) clinical deterioration suggesting that 
no further benefit from treatment is likely; 3) unacceptable adverse experiences; or 4) meets 
other criteria for discontinuation as outlined in Section 3.13 (Subject 
withdrawal/Discontinuation Criteria).  
After the end of treatment, each subject will be followed for a minimum of 30 days for 
adverse event monitoring even if the subject started new anticancer treatment. Serious 
adverse events and immune-related adverse events (irAEs) will be collected for up to 90 
days following cessation of cosibelimab treatment, or 30 days following cessation of 
treatment if the subject initiates new anticancer therapy, whichever is earlier. Subjects 
without radiographic progressive disease will have post-treatment follow-up visits for 
disease status, including radiographic imaging every 12 weeks, until initiating a non-study 
cancer treatment, experiencing disease progression, death, withdrawing consent, or 
becoming lost to follow-up. After documented disease progression each subject will be 
followed for OS until death or withdrawal of consent. 
Study Objectives: 
The primary study objective is to evaluate the antitumor activity of cosibelimab in 
combination with chemotherapy compared with chemotherapy alone using OS. 
The secondary study objectives include: 
• 
To evaluate the antitumor activity of cosibelimab in combination with 
chemotherapy compared with chemotherapy alone using investigator-assessed 
progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours 
version 1.1 (RECIST 1.1). 
• 
To evaluate the antitumor activity of cosibelimab in combination with 
chemotherapy compared with chemotherapy alone using investigator-assessed 
objective response rate (ORR) per RECIST 1.1. 
• 
To evaluate the antitumor activity of cosibelimab in combination with 
chemotherapy compared with chemotherapy alone using investigator-assessed 
duration of response (DOR) per RECIST 1.1. 
• 
To evaluate the safety and tolerability profile of cosibelimab in combination with 
pemetrexed/platinum chemotherapy. 
Subject Eligibility 
Criteria: 
Inclusion Criteria: 
All subjects enrolling into the study must meet all of the following inclusion criteria: 
1. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any 
study-specific evaluation. 
2. Age ≥ 18 years. 
3. Life expectancy of at least 3 months. 
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 
5. Have a histologically-confirmed or cytologically-confirmed diagnosis of stage IV (M1a, 
M1b or M1c- AJCC 8th edition) non-squamous NSCLC. 
6. Have confirmation that EGFR or ALK-directed therapy is not indicated (documentation 
of absence of tumor activating EGFR mutations AND absence of ALK gene 
rearrangements). 
7. Measurable disease based on RECIST 1.1 as determined by the site. Target lesions 
situated in a previously irradiated area are considered measurable if progression has 


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been demonstrated in such lesions. 
8. Have not received prior systemic treatment for their advanced/metastatic NSCLC. 
Subjects who received adjuvant or neoadjuvant therapy are eligible if the 
adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development 
of metastatic disease. 
9. Adequate organ function, confirmed by the following laboratory values: 
a. 
Neutrophils (ANC) ≥ 1500/μL. 
b. Platelets ≥ 100,000/μL. 
c. 
Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L – without tranfusions within 4 weeks of 
first dose. 
d. Creatinine or CrCL* ≤ 1.5 X upper limit of normal (ULN) OR ≥ 50 mL/min for 
subjects with creatinine levels > 1.5 X ULN.  
e. 
AST and ALT ≤ 2.5 X ULN OR 
≤ 5 X ULN for subjects with liver metastases. 
f. 
Total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total 
bilirubin levels > 1.5 X ULN. 
g. Alkaline Phosphate ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver or bone 
metastases. 
h. TSH Within normal limits. If TSH is not within normal limits at baseline, the 
subject may still be eligible if T3 and free T4 are within the normal limits. 
i. 
INR or PT ≤ 1.5 X ULN unless receiving anticoagulant therapy. 
j. 
aPTT≤ 1.5 X ULN unless receiving anticoagulant therapy. 
* Creatinine clearance (CrCl) should be calculated per institutional standard. If no local 
guideline is available, CrCL should be calculated using the Cockcroft-Gault Method):  
CrCl = ((140-age) x weight (kg) x (0.85 for females only)) / (72 x creatinine (mg/dL)). 
GFR can also be used in place of creatinine or CrCL. 
10. Have provided tumor tissue from locations not radiated prior to biopsy; formalin-fixed 
specimens after the subject has been diagnosed with metastatic disease will be preferred 
for determination of PD-L1 status prior to randomization. Biopsies obtained prior to 
receipt of adjuvant/neoadjuvant chemotherapy will be permitted if recent biopsy is not 
feasible. 
11. If female of childbearing potential (Section 3.10), have a negative urine or serum 
pregnancy test within 72 hours prior to receiving the first dose of study medication. 
12. If female of childbearing potential (Section 3.10), be willing to use an adequate method 
of contraception as outlined in Section 3.10-Contraception, for the course of the study 
through 120 days after the last dose of study medication or through 180 days after last 
dose of chemotherapeutic agents as specified in the protocol. Note: Abstinence is 
acceptable if this is the established and preferred contraception for the subject. 
13. If male subject with a female partner(s) of child-bearing potential, must agree to use an 
adequate method of contraception as outlined in Section 3.10-Contraception, starting 
with the first dose of study therapy through 180 days after the last dose of study therapy 
and chemotherapeutic agents as specified in the protocol. Males with pregnant partners 
must agree to use a condom; no additional method of contraception is required for the 
pregnant partner. Note: Abstinence is acceptable if this is the established and preferred 
contraception for the subject. 


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Exclusion Criteria: 
Any of the following criteria will exclude subjects from study participation: 
1. Has predominantly squamous cell histology NSCLC. Mixed tumors will be categorized 
by the predominant cell type; if small cell elements are present, the subject is ineligible.  
2. Is currently participating and receiving study therapy or has participated in a study of an 
investigational agent and received study therapy or used an investigational device 
within 4 weeks prior to administration of cosibelimab. 
3. Before the first dose of trial treatment: 
a. 
Has received prior systemic cytotoxic chemotherapy for metastatic disease 
b. Has received antineoplastic biological therapy (e.g., erlotinib, crizotinib, 
cetuximab) for metastatic disease 
c. 
Had major surgery (< 3 weeks prior to first dose) 
4. Received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose 
of trial treatment. 
5. Completed palliative radiotherapy within 7 days of the first dose of trial treatment. 
6. Is expected to require any other form of antineoplastic therapy while on study  
7. Has received a live-virus vaccination within 30 days of planned treatment start. 
Seasonal flu vaccines that do not contain live virus are permitted. 
8. Has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, peritoneal 
carcinomatosis. 
9. Has a known history of prior malignancy except if the subject has undergone potentially 
curative therapy with no evidence of that disease recurrence for  
5 years since initiation of that therapy. Note: The time requirement for no evidence of 
disease for 5 years does not apply to the NSCLC tumor for which a subject is enrolled 
in the study. The time requirement also does not apply to subjects who underwent 
successful definitive resection of basal cell carcinoma of the skin, superficial bladder 
cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ 
cancers. 
10. Has known active central nervous system (CNS) metastases and/or carcinomatous 
meningitis. Subjects with previously treated brain metastases may participate provided 
they are clinically stable for at least 2 weeks and, have no evidence of new or enlarging 
brain metastases and also are off steroids 3 days prior to dosing with study medication. 
Stable brain metastases by this definition should be established prior to the first dose of 
study medication. Subjects with known untreated, asymptomatic brain metastases (ie, 
no neurological symptoms, no requirements for corticosteroids, no or minimal 
surrounding edema, and no lesion > 1.5 cm) may participate but will require regular 
imaging of the brain as a site of disease. 
11. Previously had a severe hypersensitivity reaction to treatment with another monoclonal 
antibody. 
12. Has a known sensitivity to any component of cisplatin, carboplatin or pemetrexed.  
13. Has active autoimmune disease that has required systemic treatment in past  
2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive 
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form 
of systemic treatment. 
14. Immunosuppressive doses of systemic medications, such as steroids  
(doses > 10 mg/day prednisone or equivalent) must be discontinued at least  
2 weeks before study drug administration. 
15. Is on chronic systemic steroids. Subjects with asthma that require intermittent use of 
bronchodilators, inhaled steroids, or local steroid injections would not be excluded from 


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the study. 
16. Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), 
other than an aspirin dose ≤ 1.3 g per day, for a 5-day period  
(8-day period for long-acting agents, such as piroxicam). 
17. Is unable or unwilling to take folic acid or vitamin B12 supplementation. 
18. Had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody 
or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 
19. Has an active infection requiring therapy. 
20. Has known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 
antibodies positive).  
21. Has known active Hepatitis B or C or tuberculosis. Active Hepatitis B is defined as a 
known positive HBsAg result. Active Hepatitis C is defined by a known positive Hep C 
Ab result and known quantitative HCV RNA results greater than the lower limits of 
detection of the assay. 
22. Has a history or current evidence of any condition, therapy, or laboratory abnormality 
that might confound the results of the study, interfere with the subject’s participation for 
the full duration of the study, or is not in the best interest of the subject to participate, in 
the opinion of the treating Investigator. 
23. Has known psychiatric or substance abuse disorder that would interfere with 
cooperation with the requirements of the trial. 
24. Is, at the time of signing informed consent, a known regular user of any illicit drugs or 
had a recent history (within the last year) of substance abuse (including alcohol). 
25. Has symptomatic ascites or pleural effusion. A subject who is clinically stable following 
treatment for these conditions (including therapeutic thoraco- or paracentesis) is 
eligible. 
26. Has active or history of interstitial lung disease or a history of (non-infectious) 
pneumonitis that required steroids or current pneumonitis. 
27. Has had an allogeneic tissue/solid organ transplant. 
28. Any known uncontrolled or significant cardiovascular disease including, but not limited 
to any of the following: 
a. 
Myocardial infarction within 6 months. 
b. Uncontrolled angina within 3 months. 
c. 
Congestive heart failure within 3 months. 
d. Left ventricular ejection fraction (LVEF) ≤ 50%. 
e. 
Any history of clinically significant ventricular arrhythmias (such as ventricular 
tachycardia, ventricular fibrillation, or Torsades de Pointes). Controlled atrial 
fibrillation is not an exclusion criterion. 
29. Is pregnant or breastfeeding, or expecting to conceive or father children within the 
projected duration of the study. 
Study Efficacy 
Endpoints: 
The primary efficacy endpoint is OS, defined as the time from randomization to death due to 
any cause. 
The secondary efficacy endpoints include: 
• 
PFS, defined as the time from randomization to the first documented disease 
progression per RECIST 1.1 based on investigator assessment or death due to any 
cause, whichever occurs first. 
• 
ORR, defined as the proportion of subjects who have complete response or partial 
response in accordance with RECIST 1.1 based on investigator assessment. 
• 
DOR, defined as the time from first documented evidence of complete response or 
partial response until disease progression or death. 


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Data Monitoring 
Committee: 
To supplement the routine trial monitoring outlined in this protocol, an external Data 
Monitoring Committee (DMC) will monitor the interim safety data from this trial. The 
voting members of the committee are external to the Sponsor. The members of the DMC 
must not be involved with the trial in any other way (e.g., they cannot be trial investigators) 
and must have no competing interests that could affect their roles with respect to the trial. 
Statistical 
Considerations: 
Enrollment of 560 subjects is assumed to occur over 24 months at 2:1 ratio between the 
experimental and control groups. With 372 deaths at the Final Analysis (FA), the study has 
~90% power for detecting a hazard ratio (HR) of 0.7 at a type I error rate of 0.025 
(one-sided). The duration of OS in the control group is assumed to follow an exponential 
distribution with a median of 13 months based on historical data. The exponential dropout 
rate assumed for OS is 0.3% per month.  
The overall type I error rate for each efficacy endpoint included in the sequential tests is 
strictly controlled at 2.5% (one-sided). Between the endpoints, the type I error is controlled 
by the following gateway hypothesis testing procedure. First, the primary efficacy endpoint 
of OS is tested at the one-sided 0.025 level. If OS is found to be statistically significant, PFS 
will be tested using a one-sided 0.025 significance level. If PFS is found to be statistically 
significant, ORR will be tested at the one-sided 0.025 level. If OS or PFS are found to be not 
statistically significant in favor of cosibelimab combined with chemotherapy, the hypothesis 
testing procedure will stop and no further efficacy claims will be made. 
Full details of the statistical methodology for summary and analysis of data colleted in this 
study will be included in a separate Statistical Analysis Plan. 


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4. 
TRIAL FLOW CHART 
4.1. 
Initial Treatment Phase 
Details regarding the procedures listed in this table are outlined in Section 5. 
 
Screening 
Phase 
Treatment Cycles (3-Week Cycles) 
End of 
Treatment 
Post-Treatment 
Treatment Cycle 
Screening 
1 
2 
3 
4 
5 
6 to 
17 
18+ 
Discon 
Visit 
Safety 
Follow-Up 
Visit 
Follow-Up  
Visits 
Survival 
Follow-up1 
Scheduling Window (Days)2 
-28 to -1 
+ 3 
+/- 3 
+/- 3 
+/- 3 
+/- 3 
+/- 3 
+/- 3 
At Time of 
Discon  
+/- 3 days 
30 Days Post 
Discon  
+/- 3 days 
Every 6 
Weeks Post 
Safety 
Follow-up 
+/- 7 days 
Every 12 
Weeks  
+/- 14 days 
Administrative Procedures 
Informed consent14 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics/medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X13 
X13 
NSCLC disease details and prior treatment 
X 
 
 
 
 
 
 
 
 
 
 
 
Obtain allocation number using IVRS/IWRS11 
 
X 
 
 
 
 
 
 
 
 
 
 
Subsequent antineoplastic therapy status 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
Survival status1 
 
Survival status at Sponsor’s request 
X 
Clinical Procedures / Assessments 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Full physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
Directed physical examination 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs and weight 
X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECG 
X15 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance status 
X3 
X12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Laboratory Procedures / Assessments: Local Laboratory5 
Pregnancy test – urine or serum β-HCG4 
X 
 
 
 
 
 
 
 
 
 
 
 
PT/INR and aPTT/PTT5 
X3 
 
 
 
 
 
 
 
 
 
 
 
CBC with differential5 
X3 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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Screening 
Phase 
Treatment Cycles (3-Week Cycles) 
End of 
Treatment 
Post-Treatment 
Treatment Cycle 
Screening 
1 
2 
3 
4 
5 
6 to 
17 
18+ 
Discon 
Visit 
Safety 
Follow-Up 
Visit 
Follow-Up  
Visits 
Survival 
Follow-up1 
Scheduling Window (Days)2 
-28 to -1 
+ 3 
+/- 3 
+/- 3 
+/- 3 
+/- 3 
+/- 3 
+/- 3 
At Time of 
Discon  
+/- 3 days 
30 Days Post 
Discon  
+/- 3 days 
Every 6 
Weeks Post 
Safety 
Follow-up 
+/- 7 days 
Every 12 
Weeks  
+/- 14 days 
Comprehensive chemistry panel5 
X3 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Creatinine Clearance Calculation 
X3 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Urinalysis5 
X3 
 
 
 
 
 
X6 
X6 
X 
X 
 
 
TSH (with reflex to FT4, FT3)5 
X3 
 
X 
 
X 
 
X7 
X7 
X 
X 
 
 
Laboratory Procedures / Assessments: Central Laboratory 
Cosibelimab pharmacokinetics 
 
Serum collected according to schedule in Section 4.1.1 
 
 
Anti-cosibelimab antibodies 
 
Serum collected according to schedule in Section 4.1.1 
 
 
Pharmacokinetics for pemetrexed, carboplatin and 
cisplatin (30 subjects per arm) 
 
Serum collected according to 
schedule in Section 4.1.2 
 
 
 
 
 
 
 
Tumor Tissue Collection 
Tumor tissue collection for PD-L1 expression testing 
(ALK translocation and EGFR mutation testing, if 
unknown) 
X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Measurements 
Tumor imaging 
X 
 
 
X8 
 
X8 
X8 
X9 
X10 
 
X10 
 
Study Drug Administration 
Cisplatin or carboplatin 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Pemetrexed 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Cosibelimab 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
1. After documented disease progression, or the start of new anti-cancer treatment; contacts are approximately every 12 weeks by telephone. Updated survival 
status may be requested by the Sponsor at any time during the course of the study. Upon Sponsor notification, all participants who do not/will not have a 
scheduled study visit or study contact during the Sponsor defined time period will be contacted for their survival status (excluding participants who have a 
death event previously recorded).  
2. Height will be measured only at Screening. 
3. ECOG and laboratory tests for screening are to be performed within 10 days prior to the first dose of trial treatment. 


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4. For women of reproductive potential, a urine pregnancy test should be performed within 72 hours prior to first dose of trial treatment. A serum test can be 
considered if urine is not appropriate. Monthly pregnancy testing should be conducted as per local regulations where applicable. 
5. After Cycle 1, lab samples can be collected up to 3 days prior to Day 1 of subsequent cycles. 
6. To be repeated every 6 cycles beginning with Cycle 6. 
7. To be repeated every other Cycle beginning with Cycle 6. 
8. Imaging performed at 6 weeks (+/- 7 days) and 12 weeks (+/- 7 days) and then every 9 weeks (63 days ± 7 days) for the first 48 weeks in the treatment 
period. 
9. Imaging performed every 12 weeks (84 days +/- 7 days) subsequently. 
10. If a previous scan was obtained within 4 weeks prior to the date of discontinuation, then a scan at treatment discontinuation is not mandatory. Follow up visit 
scans to be performed only for subjects that discontinued NOT for progressive disease, and using the same imaging schedule used while on treatment (that 
is, every 6 or 9 weeks in year 1 or 12 weeks after year 1). 
11. Obtaining allocation number should be performed within 3 days prior to the first dose of trial treatment. 
12. Does not have to be done if Screening ECOG was performed within 3 days prior to Cycle 1. 
13. After the Safety Follow-up Visit, record all medications taken for SAEs and irAEs as defined in Section 6. 
14. May be signed before Day -28. The screening period will then start with the first study-related assessment, excluding the tumor tissue collection and 
PD-L1/ALK/EGFR testing. 
15. Following Screening, 12-lead ECG will be obtained when clinically indicated.  


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4.1.1. Pharmacokinetic and Anti-Cosibelimab Antibodies Collection Schedule for Cosibelimab 
Study Day 
Time 
(Relative to Dosing) 
PK Blood  
Sample 
Anti-cosibelimab 
Antibodies  
Blood Sample 
Cycle 1 Day 1 
0 (Predose)a 
X 
X 
 
EOIb 
X 
 
 
EOI + 60 min 
X 
 
 
EOI + 120 min 
X 
 
 
EOI + 240 min 
X 
 
Cycle 2 Day 1 
0 (Predose)a 
X 
X 
 
EOIb 
X 
 
 
EOI + 60 min 
X 
 
Cycle 4 Day 1 
0 (Predose)a 
X 
X 
 
EOIb 
X 
 
 
EOI + 60 min 
X 
 
Cycle 8 Day 1 and every eight cycles Day 1 thereafter 
0 (Predose)a 
X 
X 
Safety Follow-up Visitc 
 
X 
X 
EOI: End of Infusion. 
a 
Predose samples will be drawn within 60 minutes before infusion. PK blood samples should be taken at the same time as blood collection for 
anti-cosibelimab antibodies. 
b 
Should be drawn within 30 minutes after end of infusion. 
c 
A single sample will be taken at the Safety Follow-up Visit. 
Samples are to be drawn from a site other than the infusion site (i.e., contra lateral arm) on days of infusion. If drug was administered via a central venous 
catheter, sample collection for PK should be from a different site. 


Clinical Trial Protocol Number: CK-301-301 
Protocol Version 1.0 
 
Confidential 
Page 60 of 124 
 
4.1.2. Pharmacokinetic Collection Schedule for Pemetrexed, Carboplatin and Cisplatin 
At selected sites, a subset of 30 subjects in each arm will undergo the following additional pharmacokinetic assessments for 
pemetrexed, carboplatin and cisplatin. 
Study Day 
Time 
(Relative to Dosing) 
Pemetrexed 
Carboplatin 
Cisplatin 
Cycle 1 Day 1 
0 (Predose)a 
X 
X 
X 
 
EOIb 
X 
X 
X 
 
EOI + 30 min 
X 
 
 
 
EOI + 60 min 
X 
X 
X 
 
EOI + 120 min 
X 
X 
X 
 
EOI + 240 min 
X 
X 
X 
Cycle 2 Day 1 
0 (Predose)a 
X 
X 
X 
 
EOIb 
X 
X 
X 
 
EOI + 60 min 
X 
X 
X 
Cycle 4 Day 1 
0 (Predose)a 
X 
X 
X 
 
EOIb 
X 
X 
X 
 
EOI + 60 min 
X 
X 
X 
EOI: End of Infusion. 
a 
Predose samples will be drawn within 60 minutes before infusion.  
b 
Should be drawn within 15 minutes after end of infusion. The infusion duration for pemetrexed is 10 minutes (0.17 hour), carboplatin is 15-60 minutes, and 
cisplatin is 30 minutes.  
Samples are to be drawn from a site other than the infusion site (i.e., contra lateral arm) on days of infusion. If drug was administered via a central venous 
catheter, sample collection for PK should be from a different site.