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Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy

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ClinicalTrials.gov Identifier: NCT02680184
Recruitment Status : Recruiting
First Posted : February 11, 2016
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Checkmate Pharmaceuticals

Brief Summary:
A Multicenter, Two-Part, Open-Label, Phase 1b Clinical Study of CMP-001 in Combination with Pembrolizumab or as a Monotherapy in Subjects with Advanced Melanoma

Condition or disease Intervention/treatment Phase
Stage IV Skin Melanoma Drug: CMP-001 Drug: Pembrolizumab Phase 1

Detailed Description:

Objectives:

Primary (Part 1):

• To determine the recommended Phase 2 dose of CMP-001 when given in combination with pembrolizumab in subjects with advanced melanoma.

Primary (Part 2):

• To assess and describe the safety profile of CMP-001 when administered as monotherapy

Methodology:

This is a multicenter, open-label, Phase 1b clinical study of intratumoral administration of CMP-001 in combination with pembrolizumab or as a monotherapy in subjects with advanced melanoma. The study will be conducted in two parts. Part 1 (CMP-001 + pembrolizumab) is comprised of two phases: 1) a Dose Escalation Phase and 2) a Dose Expansion Phase. Part 2 of the study is designed to assess the CMP-001 as a monotherapy.

The Part 1 Dose Escalation phase of the study will evaluate two treatment schedules of CMP-001 (at doses of 1 mg, 3 mg, 5 mg, 7.5 mg or 10 mg) administered in combination with pembrolizumab, designated as Schedule "A" or "B". There were 44 subjects enrolled into the Part 1 Dose Escalation phase of the study.

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses) then administered once every 3 weeks until discontinuation.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until discontinuation.

The Part 1 Dose Expansion phase of the study will evaluate the recommended Phase 2 dose (RP2D) of CMP-001 + pembrolizumab on treatment Schedule A. There will be a maximum of 80 subjects enrolled in the Part 1 Dose Expansion phase.

Part 2 will evaluate CMP-001 as a monotherapy on treatment Schedule A. If the subject progresses after 8 weeks of CMP-001 monotherapy treatment they have the option to crossover onto the combination treatment of CMP-001+ pembrolizumab. There will be a maximum of 20 subjects enrolled in Part 2.

There will be a maximum of 144 patients enrolled in this study.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Two-Part, Open-Label, Phase 1B Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy in Subjects With Advanced Melanoma
Study Start Date : March 2016
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: CMP-001 1 mg plus pembrolizumab
Experimental CMP-001 in combination with pembrolizumab. CMP-001 administered intratumorally
Drug: CMP-001

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: QbG10, CYT003

Drug: Pembrolizumab

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: Keytruda

Experimental: CMP-001 3 mg plus pembrolizumab
Experimental CMP-001 in combination with pembrolizumab. CMP-001 administered intratumorally
Drug: CMP-001

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: QbG10, CYT003

Drug: Pembrolizumab

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: Keytruda

Experimental: CMP-001 5 mg plus pembrolizumab
Experimental CMP-001 in combination with pembrolizumab. CMP-001 administered intratumorally
Drug: CMP-001

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: QbG10, CYT003

Drug: Pembrolizumab

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: Keytruda

Experimental: CMP-001 7.5 mg plus pembrolizumab
Experimental CMP-001 in combination with pembrolizumab. CMP-001 administered intratumorally
Drug: CMP-001

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: QbG10, CYT003

Drug: Pembrolizumab

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: Keytruda

Experimental: CMP-001 10 mg plus pembrolizumab
Experimental CMP-001 in combination with pembrolizumab. CMP-001 administered intratumorally
Drug: CMP-001

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: QbG10, CYT003

Drug: Pembrolizumab

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: Keytruda

Experimental: Part 1 Dose Expansion CMP-001 plus pembrolizumab
Experimental CMP-001 in combination with pembrolizumab. CMP-001 administered intratumorally
Drug: CMP-001

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: QbG10, CYT003

Drug: Pembrolizumab

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: Keytruda

Experimental: CMP-001 Part 2 Monotherapy and Part 2 Crossover to Combination
Experimental CMP-001 administered intratumorally Experimental CMP-001 in combination with pembrolizumab
Drug: CMP-001

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: QbG10, CYT003

Drug: Pembrolizumab

The study is designed as two parts: Part 1 CMP-001 in combination with pembrolizumab which is comprised of two phases (1): Dose Escalation Phase (2) Dose Expansion Phase and Part 2: Monotherapy and Crossover to Combination.

The study will evaluate two schedules of CMP-001 given intratumorally, designated as Schedule "A" or "B".

  • Schedule A: CMP-001 will be administered once a week for 7 weeks (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.
  • Schedule B: CMP-001 will be administered once a week for 2 weeks, then once every 3 weeks for 5 additional doses (total of 7 doses). Thereafter it will be administered once every 3 weeks until the subject is discontinued.

Part 1 Dose Expansion and Part 2 Monotherapy will be conducted under Schedule A only.

Other Name: Keytruda




Primary Outcome Measures :
  1. Determination of the recommended Phase 2 dose of CMP-001 when given in combination with Pembrolizumab in subjects with advanced melanoma. [ Time Frame: 18 Months ]

Secondary Outcome Measures :
  1. Assessment of treatment-emergent adverse events (TEAEs), using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Consent through 30 days post End of Treatment Visit (7 days post following study completion). ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  2. Part 1 Dose Escalation: Assessment of oral temperature measured by degrees fahrenheit [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, Day 2 wks 3, 7 and every 3 wks post Wk 7, within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 wks 1, 2, 5, 8, 11, 14, 17, Day 2 wks 5, 17, and every 3 wks post wk17, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  3. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of oral temperature measured by degrees fahrenheit [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose. ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  4. Part 1 Dose Escalation: Assessment of respiratory rate measured by beats per minute [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, Day 2 wks 3, 7 and every 3 wks post Wk 7, within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 wks 1, 2, 5, 8, 11, 14, 17, Day 2 wks 5, 17, and every 3 wks post wk17, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  5. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of respiratory rate measured by beats per minute [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  6. Part 1 Dose Escalation: Assessment of systolic and diastolic blood pressure [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, Day 2 wks 3, 7 and every 3 wks post Wk 7, within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 wks 1, 2, 5, 8, 11, 14, 17, Day 2 wks 5, 17, and every 3 wks post wk17, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  7. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of systolic and diastolic blood pressure [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  8. Part 1 Dose Escalation: Assessment of weight measured by kilograms (kg) [ Time Frame: Schedule A: Screening, Day 1 on wks 1, 3, 7 and within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 on wks 1, 5, 17, and within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  9. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of weight measured by kilograms (kg) [ Time Frame: Schedule A: Screening, Day 1 on wks 1, 3, 7 and within 7 days of last CMP-001 dose. ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  10. Part 1 Dose Escalation: Assessment of Body Mass Index (BMI) measured by kg/m2 [ Time Frame: Schedule A: Screening, Day 1 on wks 1, 3, 7 and within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 on wks 1, 5, 17, and within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  11. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of Body Mass Index (BMI) measured by kg/m2 [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  12. Part 1 Dose Escalation: Perform and assess results of 12 lead electrocardiograms (ECGs) [ Time Frame: Schedule A: Screening, Day 1 on wks 1, 3, 7 and within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 on wks 1, 5, 17, and within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  13. Part 1 Dose Expansion and Part 2 Monotherapy: Perform and assess results of 12 lead electrocardiograms (ECGs) [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  14. Part 1 Dose Escalation: Assessment of clinical laboratory parameters (urinalysis) by urine sample analysis [ Time Frame: Schedule A: Screening, Day 1 on wks 1-7 and every 3 wks post Wk 7, within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 on wks 1, 2, 5, 8, 11, 14, 17, and every 3 wks post wk17, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  15. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of clinical laboratory parameters (urinalysis) by urine sample analysis [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  16. Part 1 Dose Escalation: Assessment of clinical laboratory parameters (chemistry and hematology) through blood sample analysis [ Time Frame: Schedule A: Screening, Day 1 on wks 1-7 and every 3 wks post Wk 7, within 7 days of last CMP-001 dose. Schedule B: Screening, Day 1 on wks 1, 2, 5, 8, 11, 14, 17, and every 3 wks post wk17, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab

  17. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of clinical laboratory parameters (chemistry and hematology) through blood sample analysis [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose ]
    To assess and describe the safety profile of CMP-001 when given in conjunction with Pembrolizumab or as a Monotherapy

  18. Part 1 Dose Escalation: Assessment of concentrations of the chemokine IP-10 in collected serum samples. [ Time Frame: Schedule A: Screening, Day 1 on weeks 1,3, 7 and Day 2 on Weeks 3, 7. Schedule B: Screening, Day 1 on weeks 1, 5, 17, and Day 2 on weeks 1, 5, 17 ]
    To assess and describe the pharmacodynamic effects of the addition of CMP-001 to Pembrolizumab on serum concentrations of chemokine IP-10

  19. Part 1 Dose Expansion and Part 2 Monotherapy: Assessment of concentrations of the chemokine IP-10 in collected serum samples. [ Time Frame: Schedule A: Screening, Day 1 wks 1-7, every 3 wks post Wk 7, within 7 days of last CMP-001 dose ]
    To assess and describe the pharmacodynamic effects of the addition of CMP-001 to Pembrolizumab or as a Monotherapy on serum concentrations of chemokine IP-10

  20. Assessment of antitumor activity Response Evaluation Criteria In Solid Tumors (RECIST Version 1.1) using computerized tomography (CT) or magnetic resonance imaging (MRI) scans. [ Time Frame: Screening and every 12 weeks throughout study (from W1D1) and within 7 days of last CMP-001 dose ]
    To assess and describe preliminary evidence of antitumor activity for CMP-001 when combined with Pembrolizumab or as a Monotherapy

  21. Assessment of antitumor activity Immune-Related Response Criteria (irRC) using computerized tomography (CT) or magnetic resonance imaging (MRI) scans. [ Time Frame: Screening and every 12 weeks throughout study (from W1D1) and within 7 days of last CMP-001 dose ]
    To assess and describe preliminary evidence of antitumor activity for CMP-001 when combined with Pembrolizumab or as a Monotherapy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria Part 1 (CMP-001 + pembrolizumab):

  1. Histopathologically confirmed diagnosis of metastatic, or unresectable, malignant melanoma. Ocular melanoma subjects are not eligible.
  2. Male and female subjects age 18 or older

3a. Subjects who are currently receiving treatment with any anti-PD-1/PD-L1 antibody, either alone or in combination and who are progressing. Subjects must have received at least 4 doses of anti-PD-1/PD-L1 before enrolling into the CMP-001-001 study.

OR

3b. Subjects who have previously received any anti-PD-1/PD-L1 therapy, alone or in combination and progressed, regardless of the best overall response to prior anti-PD-1/PD-L1 based therapy. Subjects must have received at least 4 doses of anti-PD-1/PD-L1.

4. Subjects must have at least one tumor lesion with a longest diameter of ≥0.5 cm that can be easily palpated or detected by ultrasound to facilitate intratumoral injection of CMP-001 (i.e., tumor in skin, muscle, subcutaneous tissue or accessible lymph node).

5. Subjects must have measurable disease by RECIST Version 1.1. 6. Capable of understanding and complying with protocol requirements. 7. A life expectancy of greater than 24 weeks at Screening. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 9. Most recent laboratory values (within 3 weeks prior to Week 1 Day 1 (W1D1)) before study entry meet the following standards:

  • Bone marrow function: neutrophil count ≥1,000/mm3, platelet count ≥ 75,000/mm3 and hemoglobin concentration > 8.0 g/dL.
  • Liver function: total bilirubin ≤ 1.5 times the upper limit of normal (ULN) ranges of each institution, with the following exception: patients with Gilbert Disease serum bilirubin > 3X ULN AND aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the ULN range of each institution.
  • LDH ≤2.0 times the ULN range of each institution
  • Renal function: serum creatinine ≤ 1.5 times the ULN range of each institution. 10. The subject must sign a written informed consent form prior to the initiation of any study procedures. Adult subjects unable to provide written informed consent on their own behalf will not be eligible for the study.

Part 1 Dose Expansion Phase subjects must also meet the following inclusion criterion:

11. At least one additional lesion that is measurable and is not intended for injection (to allow an assessment of systemic antitumor effect). These lesions not intended for injection may be located in any metastatic site.

Exclusion Criteria Part 1 (CMP-001 + pembrolizumab):

  1. Pregnant or breastfeeding.
  2. Received investigational therapy (e.g. small molecule or biologic) within 30 days prior to the start of CMP-001 dosing on W1D1. However, if an investigational therapy has a short half-life, a reduced wash out period may be acceptable with Sponsor approval.
  3. Received treatment with anti-CTLA-4 antibody within 30 days prior to the start of CMP-001 dosing on W1D1.
  4. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). If there is no known or documented history of HIV, Hepatitis B or Hepatitis C, the site is not required to do additional testing for these values at Screening.
  5. Developed autoimmune disorders of Grade 4 while on prior immunotherapy. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤ 1 and the subject has been off systemic steroids at doses > 10mg/day for at least two weeks.
  6. Require systemic pharmacologic doses of corticosteroids greater than the equivalent of 10 mg/day; replacement doses, topical, ophthalmologic and inhalational steroids are permitted. Subjects who have a history of adrenal insufficiency and are receiving greater than 10 mg/day coticosteroid may be eligible but only after Sponsor consultation. Subjects who are currently receiving steroids at a dose of ≤10 mg/day do not need to discontinue steroids prior to enrollment.
  7. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. However subjects with active CNS metastases are eligible for the trial if

    • the metastases have been treated by surgery and/or radiotherapy,
    • the subject is off corticosteroids > 10 mg/day and is neurologically stable for at least 2 weeks prior to Screening.
    • brain MRI completed within 3 months of screening (required for all subjects).
  8. Any concurrent uncontrolled illness, including mental illness or substance abuse, which in the opinion of the Investigator, would make the subject unable to cooperate or participate in the trial.
  9. Severe uncontrolled cardiac disease within 6 months of Screening, including but not limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or cerebrovascular accident (CVA).
  10. Requires prohibited treatment (i.e., non-protocol specified anticancer pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant tumor).
  11. Women of child-bearing potential who are unable or unwilling to use an acceptable method of contraception.

Inclusion Criteria - Part 2: CMP-001 Monotherapy

Subjects must meet all of the following inclusion criteria to be eligible:

  1. Histopathologically confirmed diagnosis of metastatic, or unresectable, malignant melanoma. Ocular melanoma subjects are not eligible.
  2. Male or female subjects age 18 or older.
  3. Previously received any anti-PD-1/PD-L1 therapy, alone or in combination. Subjects must have received a minimum of 4 doses of anti-PD-1/PD-L1 therapy prior to study entry.
  4. Subjects must have at least one tumor lesion with a longest diameter of ≥0.5 cm that can be easily palpated or detected by ultrasound to facilitate intratumoral injection of CMP-001 (i.e., tumor in skin, muscle, subcutaneous tissue or accessible lymph node).
  5. Subjects must have measurable disease by RECIST Version 1.1.
  6. Capable of understanding and complying with protocol requirements.
  7. A life expectancy of greater than 24 weeks at Screening.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
  9. Most recent laboratory values (within 3 weeks prior to first CMP-001 injection at Week 1 Day 1 (W1D1)) before study entry meet the following standards:

    • Bone marrow function: neutrophil count ≥1,000/mm3, platelet count ≥75,000/mm3 and hemoglobin concentration > 8.0 g/dL.
    • Liver function: total bilirubin ≤ 1.5 times the upper limit of normal (ULN) ranges of each institution, aspartate aminotransferase and alanine aminotransferase ≤ 3 times the ULN range of each institution.
    • LDH ≤2.0 times the ULN range of each institution.
    • Renal function: serum creatinine ≤1.5 times the ULN range of each institution.
  10. The subject must sign a written informed consent form prior to the initiation of any study procedures. Adult subjects unable to provide written informed consent on their own behalf will not be eligible for the study.

Exclusion Criteria Part 2: (CMP-001 Monotherapy)

  1. Pregnant or breastfeeding.
  2. Received investigational therapy (e.g. small molecule or biologic) within 30 days prior to the start of CMP-001 dosing on W1D1. Received prior therapy with an anti-PD1/PD-L1 or anti-CTLA-4 within 45 days prior to the start of CMP-001 dosing on W1D1. However, if an investigational therapy has a short half-life, a reduced wash out period may be acceptable with Sponsor approval.
  3. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). If there is no known or documented history of HIV, Hepatitis B or Hepatitis C, the site is not required to do additional testing for these values at Screening.
  4. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤1 and the subject has been off systemic steroids at doses >10 mg/day for at least 2 weeks.
  5. Require systemic pharmacologic doses of corticosteroids greater than the equivalent of 10 mg/d; replacement doses, topical, ophthalmologic and inhalational steroids are permitted. Subjects who have a history of adrenal insufficiency and are receiving greater than 10 mg/day of corticosteroid may be eligible but only after Sponsor consultation. Subjects who are currently receiving steroids at a dose of ≤ 10 mg/day do not need to discontinue steroids prior to enrollment.
  6. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. However, subjects with active CNS metastases are eligible for the trial if:

    • the metastases have been treated by surgery and/or radiotherapy.
    • the subject is off corticosteroids >10 mg/day and is neurologically stable for at least 2 weeks prior to Screening.
    • brain MRI completed within 3 months of screening (required for all subjects).
  7. Any concurrent uncontrolled illness, including mental illness or substance abuse, which in the opinion of the Investigator, would make the subject unable to cooperate or participate in the trial.
  8. Severe uncontrolled cardiac disease within 6 months of Screening, including but not limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or cerebrovascular accident (CVA).
  9. Requires prohibited treatment (i.e., non-protocol specified anticancer pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant tumor).
  10. Women of childbearing potential who are unable or unwilling to use an acceptable method of contraception.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02680184


Contacts
Contact: Dave Mauro, MD, PhD dmauro@checkmatepharma.com
Contact: Connacht Peterson, M.S. 7817185121 cpeterson@checkmatepharma.com

Locations
United States, Arizona
Banner Recruiting
Phoenix, Arizona, United States, 85006
University of Arizona Recruiting
Tucson, Arizona, United States, 85721
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Adil Daud, MD         
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
United States, District of Columbia
Georgetown Recruiting
Washington, District of Columbia, United States, 02007
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
University of Pittsburg Recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, West Virginia
West Virginia University Recruiting
Morgantown, West Virginia, United States, 26506
Sponsors and Collaborators
Checkmate Pharmaceuticals
Investigators
Principal Investigator: Mohammed Milhem University of Iowa

Responsible Party: Checkmate Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02680184     History of Changes
Other Study ID Numbers: CMP-001-001
First Posted: February 11, 2016    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Checkmate Pharmaceuticals:
Malignant melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Antineoplastic Agents