Pembrolizumab and Paclitaxel in Refractory Small Cell Lung Cancer (MISP-MK3475)

• ClinicalTrials.gov Identifier: NCT02551432
• Recruitment Status: Completed
• First Posted: September 16, 2015
• Results First Posted: February 10, 2020
• Last Update Posted: February 10, 2020
• Sponsor: Seoul National University Hospital
• Information provided by (Responsible Party): Bhumsuk Keam, Seoul National University Hospital

Tracking Information

• First Submitted Date: July 7, 2015
• First Posted Date: September 16, 2015
• Results First Submitted Date: November 25, 2019
• Results First Posted Date: February 10, 2020
• Last Update Posted Date: February 10, 2020
• Study Start Date: September 2015
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2020)

Objective Response Rate [ Time Frame: 3 months ]

Tumor response will be assessed based on modified RECIST 1.1

Original Primary Outcome Measures (submitted: September 15, 2015)

Response rate, NCI CTCAE [ Time Frame: 3 months ]

Intravenous administration of pembrolizumab and paclitaxel has clinically meaningful benefit in RR based on RECIST v1.1 One cycle of paclitaxel prior to pembrolizumab can play a role as an inducer of PD-L1 expression of tumor

Current Secondary Outcome Measures (submitted: February 7, 2020)

• Progression-free Survival [ Time Frame: from first dose to disease progression or death due to any cause, whichever came first, up to 24months ]
  Tumor response will be assessed based on modified RECIST 1.1
• Overall Response (OS) [ Time Frame: from first dose to death due to any cause, whichever came first, assessed up to 24 months ]
  Tumor response will be assessed based on modified RECIST 1.1
• Safety(Toxicity) [ Time Frame: 3 months ]
  Safety will be assessed for all subjects and documented according to the CTCAE v4.0

Original Secondary Outcome Measures (submitted: September 15, 2015)

• PFS, NCI CTCAE [ Time Frame: 3 months ]
  Intravenous administration of Pembrolizumab and paclitaxel has clinically meaningful benefit in PFS and OS based on RECIST and irRECIST
• OS, NCI CTCAE [ Time Frame: 3 months ]
  meaningful benefit in PFS and OS based on RECIST and irRECIST
• toxicity (meaningful benefit in PFS and OS based on RECIST and irRECIST) [ Time Frame: 3 months ]
  meaningful benefit in PFS and OS based on RECIST and irRECIST

Current Other Pre-specified Outcome Measures (submitted: February 7, 2020)

Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 months ]

find out predictive biomarker for pembrolizumab. Factors potentially associated with pembrolizumab response will b analyzed for providing the rationale for future patient selection.

Original Other Pre-specified Outcome Measures (submitted: September 15, 2015)

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 months ]

find out predictive biomarker for pembrolizumab. Factors potentially associated with pembrolizumab response will b analyzed for providing the rationale for future patient selection.

Descriptive Information

• Brief Title: Pembrolizumab and Paclitaxel in Refractory Small Cell Lung Cancer
• Official Title: Phase II Study of Pembrolizumab and Paclitaxel in Refractory Small Cell Lung Cancer
• Brief Summary: Patients with refractory SCLC. Patients will be treated with paclitaxel and pembrolizumab.
• Detailed Description: Open, uncontrolled, multi-center, phase II study.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Cancer

Intervention

Drug: pembrolizumab, paclitaxel

pembrolizumab, paclitaxel

Other Name: keytruda, taxol

Study Arms

Experimental: Paclitaxel pembrolizumab

• PD-L1 Induction phase : Paclitaxel 175 mg/m2, Day 1 q 3weeks, intravenous,
• Post Induction treatment phase: Paclitaxel 175 mg/m2, Day 1 q 3weeks (maximum up to total 6 cycles) + pembrolizumab 200 mg D1 q 3 weeks, intravenous,
• Maintenance phase: pembrolizumab 200 mg D1 q 3 weeks, intravenous till PD or unacceptable toxicity

Intervention: Drug: pembrolizumab, paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 15, 2015): 26
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 2018
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial.
2. Be 20 years of age on day of signing informed consent.
3. Have measurable lesions based on RECIST 1.1.
4. Have provided tissue from an archival tissue sample obtained after the last previous treatment or newly obtained core or excisional biopsy of a tumor lesion.
5. Have a performance status of 0 or 1 on the ECOG Performance Scale.

6. Demonstrate adequate organ function as defined below 'adequate organ fuction laboratory values', all screening labs should be performed within 10 days of treatment initiation.

   'adequate organ fuction laboratory values' System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L Renal Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl)≤1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels >1.5 X institutional ULN Hepatic Serum total bilirubin≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR

   • 5 X ULN for subjects with liver metastases Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
   • 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard.
7. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
8. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
9. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

   • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
   • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
7. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
12. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
13. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). (inactive HBsAg carriers with prophylactic antiviral agent are allowed)
16. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
17. Has a known history of active TB (Bacillus Tuberculosis)
18. Has known hypersensitivity to MK-3475 or any of its excipients

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT02551432
• Other Study ID Numbers: MISP MK3475
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bhumsuk Keam, Seoul National University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Seoul National University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Bhumsuk Keam, Ph.D; Seoul National University Hospital

• PRS Account: Seoul National University Hospital
• Verification Date: February 2020