Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03480230
• Date of registration: 14/03/2018
• Prospective Registration: Yes
• Primary sponsor: Arafat Tfayli
• Public title: Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer
• Scientific title: Phase II Trial of Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer
• Date of first enrolment: June 26, 2018
• Target sample size: 60
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03480230
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Jordan, Lebanon

Contacts

• Name: Arafat H Tfayli, MD
• Affiliation: American University of Beirut Medical Center

• Name: Arafat H Tfayli, MD

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Males and females aged = 18 years.

2. Histologically confirmed NSCLC (squamous and non-squamous).

3. High-risk stage IB (tumor = 4 cm in size, or grade 3, or with visceral pleura
involvement), II or IIIA disease.

4. Have biopsy tissue available (fresh and archived) for PD-L1 and correlative studies
testing prior to therapy.

5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of =

1. 6) Have a life expectancy of = 6 months. 7) No previous systemic anticancer therapy or
surgical resection for his or her NSCLC. 8) Subject has voluntarily agreed to participate
by giving written informed consent for the trial. 9) Subject must be willing and able to
comply with scheduled visits, treatment schedule and laboratory testing. 10) Female
subjects of childbearing potential must have a negative urine or serum pregnancy test
within 24 hours prior to receiving the first dose of study medication. 11) Females should
not be breastfeeding. 12) Female subjects of childbearing potential as well as males
sexually active with women of childbearing potential must be willing to use an adequate
method of contraception. 13) Have pulmonary and cardiac function testing deemed adequate
for thoracic surgical intervention. 14) Have adequate organ function by meeting the
following:

1. Absolute neutrophil count (ANC) =1,500/mcL.

2. Platelets =100,000/mcL.

3. Hemoglobin =9 g/dL.

4. Serum creatinine =1.5 X upper limit of normal (ULN) OR calculated creatinine clearance
(CrCl) (GFR can also be used in place of creatinine or CrCl) =60 mL/min for subjects
with creatinine levels > 1.5 X institutional ULN.

5. Serum total bilirubin = ULN.

6. AST (SGOT) and ALT (SGPT) = 1.5 X ULN.

7. Alkaline phosphatase = 2.5 X ULN.

8. International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5 X ULN unless the
subject is receiving anticoagulant therapy.

9. Activated Partial Thromboplastin Time (aPTT) =1.5 X ULN unless the subject is
receiving anticoagulant therapy.

Exclusion Criteria:

1. Subject deemed unfit for surgery (by pulmonary or cardiac assessment).

2. Subject with known autoimmune disease that has required systemic therapy in the last 2
years.

3. Prior organ transplantation including allogenic stem-cell transplantation.

4. Clinically significant (i.e. active) cardiovascular disease: cerebral vascular
accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
prior to enrollment), unstable angina, congestive heart failure (= New York Heart
Association Classification Class II), or serious cardiac arrhythmia requiring
medication.

5. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however,
alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety
risk based on investigator's judgment are acceptable.

6. Subject on immunosuppressive therapy or corticosteroids within 14 days prior to
starting study drugs.

7. Subject with interstitial lung disease that is symptomatic or history of pneumonitis
that required oral or systemic glucocorticoids to manage.

8. Subject must have recovered from the effects of major surgery or significant trauma at
least 14 days prior to therapy.

9. Subject with previous malignancies are excluded unless complete remission was achieved
at least 2 years prior to therapy.

10. Other active malignancy requiring concurrent intervention.

11. Subject with active infection requiring systemic therapy.

12. Subject with known history of testing positive for human immunodeficiency virus (HIV)
or known to have acquired immunodeficiency syndrome (AIDS).

13. Subject has known active hepatitis B or C.

14. Vaccination within 4 weeks of the first dose of Compound 121564 and while on trials is
prohibited except for administration of inactivated vaccines.

15. Subject is pregnant or breastfeeding.

16. Subject has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

17. Subject previously had a severe hypersensitivity reaction to any of the study drugs.

18. Subject is currently participating and receiving study therapy from another clinical
trial.

19. Subject had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an
antibody targeting other immuno-regulatory receptors or mechanisms.

20. Patient who is not willing to sign the consent form.

21. Legal incapacity or limited legal capacity patients receiving other oncology specific
medication not authorized in the protocol.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-Small Cell Lung Cancer Stage

Intervention(s)

Drug: Compound 121564

Primary Outcome(s)

Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria [Time Frame: At week 9]

Secondary Outcome(s)

Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria in enrolled squamous vs. non-squamous lung cancer patients [Time Frame: At week 9]

Overall Survival (OS) in patients with 50% or more PD-L1 vs. patients with less than 50% PD-L1 [Time Frame: At 1, 2 and 3 years]

Overall Survival (OS) [Time Frame: At 1, 2 and 3 years]

Major pathologic response rate (<10% viable tumor cells) [Time Frame: At 12 weeks]

Pathologic complete response rate [Time Frame: At 12 weeks]

Progression-Free Survival (PFS) in enrolled squamous vs. non-squamous lung cancer patients [Time Frame: At 1, 2 and 3 years]

Number of participants with treatment-related adverse events as assessed by CTCAE v 4.0 [Time Frame: With every administration]

Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria in patients with 50% or more PD-L1 vs. patients with less than 50% PD-L1 [Time Frame: At week 9]

Overall Survival (OS) in enrolled squamous vs. non-squamous lung cancer patients [Time Frame: At 1, 2 and 3 years]

Progression-Free Survival (PFS) in patients with 50% or more PD-L1 vs. patients with less than 50% PD-L1 [Time Frame: At 1, 2 and 3 years]

Patient-related outcomes Quality of Life assessment using the questionnaire for functional assessment of cancer therapy for patients with lung cancer (FACT-L version 4) [Time Frame: At week 9]

Progression-Free Survival (PFS) [Time Frame: At 1, 2 and 3 years]

Secondary ID(s)

BIO-2017-0467

MS100070_0020

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Phoenix Clinical Research

Merck KGaA, Darmstadt, Germany