PembroMab: Pembrolizumab and Monoclonal Antibody Therapy in Advanced Cancer

• Sponsor: Western Regional Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02318901
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 3
• Actual Duration (Months): 46
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

There will be two phase II cohorts for pembro plus trastuzumab: one cohort will be for patients with unresectable HER2 overexpressing gastric or GEJ cancers, the other cohort will be for patients with HER2 overexpressing metastatic breast cancer (MBC). The pembro plus ado-trastuzumab emtansine phase II arm will be for patients with HER2 overexpressing MBC. There will be two phase II cohorts for pembro plus cetuximab: one cohort will be for patients with HNSCC, the other cohort will be for patients with K-ras, B-raf, N-ras wildtype metastatic CRC.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer; Breast Cancer; Gastric Cancer; Esophageal Cancer; Colorectal Cancer	Drug: Pembrolizumab; Drug: Trastuzumab; Drug: ado-trastuzumab emtansine; Drug: Cetuximab	Phase 1/Phase 2

Detailed Description

Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Pembrolizumab will be infused prior to the start of the assigned monoclonal antibody (Mab) arm. .

Dosing for the Mab arms will begin as follows:

Arm 1: Cycle length is 21 days. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days.

Arm 2: Cycle length is 21 days. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days.

Arm 3: Cycle length is 21 days. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib/II Study of Pembrolizumab and Monoclonal Antibody Therapy in Patients With Advanced Cancer (PembroMab
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days.	Drug: Pembrolizumab; Other Names: KEYTRUDA ; Drug: Trastuzumab; Other Names: Herceptin
Experimental: Arm 2 Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days.	Drug: Pembrolizumab; Other Names: KEYTRUDA ; Drug: ado-trastuzumab emtansine; Other Names: Kadcyla
Experimental: Arm 3 Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days.	Drug: Pembrolizumab; Other Names: KEYTRUDA ; Drug: Cetuximab; Other Names: Erbitux

Outcome Measures

Primary Outcome Measures

1. Determine the Recommended Phase 2 Dose (RP2D) of Monoclonal Antibody Therapy (Mab) in Combination With Pembrolizumab (Pembro) in Subjects With Advanced Cancer [3 weeks]

   PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.

Secondary Outcome Measures

1. Frequency of Grade 3 or Higher Treatment-related Adverse Events by CTCAE 4.03 [up to 12 months]

   PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.

2. Response Rate by irRC and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria [12 weeks]

   PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.

3. To Determine the Overall Survival (OS) and Progression-free Survival (PFS) [up to 12 months]

   PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.

4. To Characterize Changes in Circulating Tumor DNA in Patients Enrolled on This Study [up to 12 months]

   PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.

5. Textural Changes Identified on Imaging That is Done Per Routine Practice [12 weeks]

   PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patient has definitive histologically or cytologically confirmed unresectable or metastatic solid tumor.

2. Patient has one or more tumor measurable as defined by RECIST 1.1 by CT scan (or PET/CT, if patient is allergic to CT contrast media).

3. Patients can be enrolled only on one of the treatment arms on this trial.

4. The investigator will select the appropriate treatment arm for the patient with the following requirements: (a) Patients cannot have had prior progression or intolerance to a specific Mab and then enrolled on an arm with that same Mab plus pembro, (b) The Mab on the arm selected must be considered standard of care or listed in the NCCN guidelines (www.nccn.org) for that cancer type. For Arm 1, patients with HER2 overexpressing MBC eligible for maintenance trastuzumab are allowed after taxane plus trastuzumab plus pertuzumab combination therapy.

5. Have recovered from acute toxicities of prior treatment:

6. 3 weeks must have elapsed since receiving any investigational agent.

7. 2 weeks must have elapsed since receiving any radiotherapy, or ≥ 3 weeks or 5 half-lives whichever is shorter for treatment with cytotoxic or biologic agents ( ≥ 6 weeks for mitomycin or nitrosoureas). Chronic treatment with non-investigational gonadotropin-releasing hormone analogs or other hormonal or supportive care is permitted.

8. Patient has adequate biological parameters as demonstrated by the following blood counts at time of screening:

9. Absolute neutrophil count (ANC) > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 9 g/dL.

10. Serum creatinine ≤2.0, total bilirubin ≤ 2 mg/dL, AST/ALT ≤ 5 times the upper limit of normal (ULN) range

11. Thyroid stimulating hormone (TSH) within institutional normal limits. If TSH is above the upper limit of normal range, then a free T4 within institutional normal limits is acceptable.

12. Persistent prior systemic therapy non-hematologic AE grade ≥ 2 (except alopecia or correctable electrolyte abnormality with supplementation)

13. Patient has a Karnofsky performance status (KPS) ≥ 70.

14. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier method) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial.

Inclusion criteria for Phase II only:

1. Patients must have unresectable HER2 overexpressing gastric or GEJ cancers to be enrolled on Cohort 1 of the pembro plus trastuzumab phase II portion.

2. Patients must have HER2 overexpressing MBC to be enrolled on Cohort 2 of the pembro plus trastuzumab phase II portion.

3. Patients must have HER2 overexpressing MBC to be enrolled on pembro plus ado-trastuzumab emtansine phase II portion.

4. Patients must have HNSCC to be enrolled on Cohort 1 of the pembro plus cetuximab phase II portion.

5. Patients must have K-ras, B-raf, N-ras wildtype CRC to be enrolled on Cohort 2 of the pembro plus cetuximab phase II portion.

Exclusion Criteria:

1. Active clinically serious infection > CTCAE (version 4.03) Grade 2.

2. Serious non-healing wound, ulcer, or bone fracture.

3. Patient has known brain metastases, unless previously treated and well-controlled for at least 1 month (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).

4. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements.

5. Patient has known active infection with HIV, hepatitis B, or hepatitis C (patients are NOT required to be tested for the presence of such viruses prior to therapy on this protocol).

6. Requiring daily corticosteroid dose ≥ 10 mg prednisone or equivalent per day.

7. Patient has undergone major surgery, other than diagnostic surgery (e.g., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.

8. Patient has a history of allergy or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the events outlined in the Contraindication or Special Warnings and Precautions sections of the product or comparator SmPC or Prescribing Information.

9. Patient has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the patient's safety or the study data integrity.

10. Patient will be receiving any other anti-cancer therapy during participation in this trial.

11. Prior treatment with pembro. Receipt of other PD-1 inhibitors or PD-L1 inhibitors is allowed.

12. Active or prior documented autoimmune disease requiring systemic treatment within the past 2 years.

Exclusion Criteria for phase II portion only:

1. Patients with a history of more than one primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the 2 years prior to enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Western Regional Medical Center/Cancer Treatment Center of America	Goodyear	Arizona	United States	85338

Sponsors and Collaborators

• Western Regional Medical Center

Investigators

• Study Director: Jordan Waypa, FNP, Western Regional Medical Center
• Principal Investigator: Alan Tan, MD, Western Regional Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 21, 2016

More Information

Publications

None provided.

• Responsible Party: Western Regional Medical Center
• ClinicalTrials.gov Identifier: NCT02318901
• Other Study ID Numbers: PembroMab
• First Posted: Dec 17, 2014
• Last Update Posted: Oct 21, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Neoplasms; Pembrolizumab; Trastuzumab; Cetuximab; Ado-Trastuzumab Emtansine; Maytansine

Study Results

Participant Flow

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
Period Title: Overall Study
STARTED	5	1	10
COMPLETED	0	0	0
NOT COMPLETED	5	1	10

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Arm 3	Total
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab	Total of all reporting groups
Overall Participants	5	1	10	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	1 100%	10 100%	16 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	52	62	58	57
Sex: Female, Male (Count of Participants)
Female	1 20%	0 0%	10 100%	11 68.8%
Male	4 80%	1 100%	0 0%	5 31.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	5 100%	1 100%	10 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Determine the Recommended Phase 2 Dose (RP2D) of Monoclonal Antibody Therapy (Mab) in Combination With Pembrolizumab (Pembro) in Subjects With Advanced Cancer
Description	PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
Measure Participants	0	0	0

2. Secondary Outcome

Title	Frequency of Grade 3 or Higher Treatment-related Adverse Events by CTCAE 4.03
Description	PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

No data was analyzed for this trial. PI left site unexpectedly.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
Measure Participants	0	0	0

3. Secondary Outcome

Title	Response Rate by irRC and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria
Description	PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

No data was analyzed for this trial. PI left site unexpectedly.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
Measure Participants	0	0	0

4. Secondary Outcome

Title	To Determine the Overall Survival (OS) and Progression-free Survival (PFS)
Description	PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

No data was analyzed for this trial. PI left site unexpectedly.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
Measure Participants	0	0	0

5. Secondary Outcome

Title	To Characterize Changes in Circulating Tumor DNA in Patients Enrolled on This Study
Description	PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

No data was analyzed for this trial. PI left site unexpectedly.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
Measure Participants	0	0	0

6. Secondary Outcome

Title	Textural Changes Identified on Imaging That is Done Per Routine Practice
Description	PI left site. Study was prematurely terminated. No additional study items were conducted including, data collection, results or statistical analysis completed.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

No data was analyzed for this trial. PI left site unexpectedly.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
Measure Participants	0	0	0

Adverse Events

Time Frame	PI no longer at site. Results not collected
Adverse Event Reporting Description	PI no longer at site. Results not collected
Arm/Group Title	Arm 1		Arm 2		Arm 3
Arm/Group Description	Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days. Pembrolizumab Trastuzumab		Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days. Pembrolizumab ado-trastuzumab emtansine		Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days. Pembrolizumab Cetuximab
All Cause Mortality
	Arm 1		Arm 2		Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Arm 1		Arm 2		Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2		Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.