Testing Ado-Trastuzumab Emtansine as a Potential Targeted Treatment in Cancers With HER2 Genetic Changes (MATCH-Subprotocol Q)

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04439110
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arm: 1

Study Details

Study Description

Brief Summary

This phase II MATCH treatment trial identifies the effects of ado-trastuzumab emtansine in patients whose cancer has a genetic change called HER2 amplification. Ado-trastuzumab emtansine is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called DM1. Trastuzumab is a form of "targeted therapy", because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors and delivers DM1 to kill them. Researchers hope to learn if the study drug will shrink this type of cancer or stop its growth.

Condition or Disease	Intervention/Treatment	Phase
Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma	Biological: Trastuzumab Emtansine	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

1. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

2. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

3. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MATCH Treatment Subprotocol Q: Ado-trastuzumab Emtansine in Patients With Tumors With HER2 Amplification (Except Breast and Gastric/Gastro-Esophageal Junction (GEJ) Adenocarcinomas)
• Actual Study Start Date: Aug 12, 2015
• Actual Primary Completion Date: Mar 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (trastuzumab emtansine) Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Biological: Trastuzumab Emtansine; Given IV; Other Names: Ado Trastuzumab Emtansine ADO-Trastuzumab Emtansine Kadcyla PRO132365 RO5304020 T-DM1 Trastuzumab-DM1 Trastuzumab-MCC-DM1 Trastuzumab-MCC-DM1 Antibody-Drug Conjugate Trastuzumab-MCC-DM1 Immunoconjugate

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [Tumor assessments occurred at baseline, then every 3 cycles for the first 33 cycles and every 4 cycles thereafter until disease progression, up to 3 years post registration]

   ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

Secondary Outcome Measures

1. 6 Months Progression-free Survival (PFS) Rate [Assessed at baseline, then every 3 cycles for the first 33 cycles and every 4 cycles thereafter until disease progression, up to 3 years post registration]

   Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.

2. Progression Free Survival (PFS) [Assessed at baseline, then every 3 cycles for the first 33 cycles and every 4 cycles thereafter until disease progression, up to 3 years post registration]

   Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Median PFS will be estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

• Patients' tumor sample must have HER2 amplification > 7 based on targeted custom Ampliseq panel on the Ion Torrent Personal Genome Machine (PGM)

• Hemoglobin >= 9.0 g/dL (which may be reached by transfusion)

• Patients will be allowed if on anticoagulation (except warfarin and other coumarin derivatives) or on aspirin 81 mg by mouth daily. Additional monitoring while on anticoagulation will be based on institutional guidelines and/or physician discretion. However, patients will not be allowed if on long acting anti-platelet agents such as clopidogrel

• Patients must have an electrocardiogram (ECG) within 4 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

• Patients must have echocardiography (ECHO) or nuclear study (multigated acquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < 50% to be eligible

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after completion of study

Exclusion Criteria:

• Patients with a diagnosis of breast cancer or gastric/gastroesophageal junction (GEJ) cancer will be excluded

• Patients must not have known hypersensitivity to ado-trastuzumab emtansine or compounds of similar chemical or biologic composition

• Patients with current peripheral neuropathy of grade 3 or greater (National Cancer Institute [NCI]-Common Toxicity Criteria [CTC], version 4.0) will be excluded

• Neuropathy assessment and grade assignment will be based on history (location, duration, balance and gait, effect on activity of daily living [ADLs]) and physical exam

• Patient must not have had any of the prior therapies:

• Food and Drug Administration (FDA) approved:

• Trastuzumab

• Pertuzumab

• Ado-trastuzumab emtansine

• Investigational:

• Margetuximab

• PF-05280014 (Pfizer, Trastuzumab Biosimilar)

• CT-P6 (Celltrion, Trastuzumab Biosimilar)

• ABP-980 (Amgen, Trastuzumab Biosimilar)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ECOG-ACRIN Cancer Research Group	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Komal Jhaveri, ECOG-ACRIN Cancer Research Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 28, 2020

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT04439110
• Other Study ID Numbers: NCI-2020-02979; NCI-2020-02979; EAY131-Q; EAY131-Q; U10CA180820; U24CA196172
• First Posted: Jun 19, 2020
• Last Update Posted: Jul 19, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Lymphoma; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine; Immunoconjugates

Study Results

Participant Flow

Recruitment Details	Subprotocol Q was activated on August 12, 2015. A total of 58 patients were assigned to this arm after screening, all from screening cohort. Of the 58 patients, 38 patients were enrolled to arm Q between November 19, 2015 and March 20, 2017.
Pre-assignment Detail	To be assigned to a specific MATCH subprotocol, patients needed to submit a tumor biopsy for molecular characterization and those with molecular variants addressed by treatments included in the trial entered corresponding MATCH subprotocol. For the subprotocol Q, patients had to have a tumor ERBB2 copy number of >7.

Arm/Group Title	Treatment (Trastuzumab Emtansine)
Arm/Group Description	Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Trastuzumab Emtansine: Given IV
Period Title: Overall Study
STARTED	38
Eligible	36
COMPLETED	0
NOT COMPLETED	38

Baseline Characteristics

Arm/Group Title	Treatment (Trastuzumab Emtansine)
Arm/Group Description	Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Trastuzumab Emtansine: Given IV
Overall Participants	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	23 63.9%
Male	13 36.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.6%
Not Hispanic or Latino	31 86.1%
Unknown or Not Reported	3 8.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.8%
Asian	2 5.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 13.9%
White	26 72.2%
More than one race	0 0%
Unknown or Not Reported	2 5.6%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.
Time Frame	Tumor assessments occurred at baseline, then every 3 cycles for the first 33 cycles and every 4 cycles thereafter until disease progression, up to 3 years post registration

Outcome Measure Data

Analysis Population Description

Patients who were eligible and received protocol treatment

Arm/Group Title	Treatment (Trastuzumab Emtansine)
Arm/Group Description	Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Trastuzumab Emtansine: Given IV
Measure Participants	36
Number (90% Confidence Interval) [percentage of participants]	2 5.6%

2. Secondary Outcome

Title	6 Months Progression-free Survival (PFS) Rate
Description	Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
Time Frame	Assessed at baseline, then every 3 cycles for the first 33 cycles and every 4 cycles thereafter until disease progression, up to 3 years post registration

Outcome Measure Data

Analysis Population Description

Patients who were eligible and received protocol treatment

Arm/Group Title	Treatment (Trastuzumab Emtansine)
Arm/Group Description	Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Trastuzumab Emtansine: Given IV
Measure Participants	36
Number (90% Confidence Interval) [percentage of participants]	23.6 65.6%

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Median PFS will be estimated using the Kaplan-Meier method.
Time Frame	Assessed at baseline, then every 3 cycles for the first 33 cycles and every 4 cycles thereafter until disease progression, up to 3 years post registration

Outcome Measure Data

Analysis Population Description

Patients who were eligible and received protocol treatment

Arm/Group Title	Treatment (Trastuzumab Emtansine)
Arm/Group Description	Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Trastuzumab Emtansine: Given IV
Measure Participants	36
Median (90% Confidence Interval) [months]	3.1

Adverse Events

Time Frame	Assessed every 21 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration.
Arm/Group Title	Treatment (Trastuzumab Emtansine)
Arm/Group Description	Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Trastuzumab Emtansine: Given IV
All Cause Mortality
	Treatment (Trastuzumab Emtansine)
	Affected / at Risk (%)	# Events
Total	30/38 (78.9%)
Serious Adverse Events
	Treatment (Trastuzumab Emtansine)
	Affected / at Risk (%)	# Events
Total	12/38 (31.6%)
Blood and lymphatic system disorders
Anemia	3/38 (7.9%)
Eye disorders
Blurred vision	1/38 (2.6%)
Gastrointestinal disorders
Diarrhea	1/38 (2.6%)
Ileal obstruction	1/38 (2.6%)
Nausea	1/38 (2.6%)
General disorders
Fatigue	2/38 (5.3%)
Fever	1/38 (2.6%)
Infections and infestations
Sepsis	1/38 (2.6%)
Upper respiratory infection	1/38 (2.6%)
Urinary tract infection	1/38 (2.6%)
Injury, poisoning and procedural complications
Fall	1/38 (2.6%)
Investigations
Alkaline phosphatase increased	1/38 (2.6%)
Aspartate aminotransferase increased	1/38 (2.6%)
Lymphocyte count decreased	1/38 (2.6%)
Neutrophil count decreased	1/38 (2.6%)
Platelet count decreased	2/38 (5.3%)
Investigations - Other, specify	1/38 (2.6%)
Metabolism and nutrition disorders
Anorexia	1/38 (2.6%)
Dehydration	2/38 (5.3%)
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	1/38 (2.6%)
Renal and urinary disorders
Hematuria	1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/38 (2.6%)
Hypoxia	1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Treatment (Trastuzumab Emtansine)
	Affected / at Risk (%)	# Events
Total	29/38 (76.3%)
Blood and lymphatic system disorders
Anemia	9/38 (23.7%)
Gastrointestinal disorders
Constipation	2/38 (5.3%)
Dry mouth	2/38 (5.3%)
Mucositis oral	2/38 (5.3%)
Nausea	8/38 (21.1%)
Vomiting	8/38 (21.1%)
General disorders
Chills	2/38 (5.3%)
Edema limbs	3/38 (7.9%)
Fatigue	14/38 (36.8%)
Fever	3/38 (7.9%)
Gait disturbance	2/38 (5.3%)
Immune system disorders
Allergic reaction	2/38 (5.3%)
Investigations
Alanine aminotransferase increased	4/38 (10.5%)
Alkaline phosphatase increased	6/38 (15.8%)
Aspartate aminotransferase increased	11/38 (28.9%)
Blood bilirubin increased	3/38 (7.9%)
Creatinine increased	3/38 (7.9%)
Lymphocyte count decreased	2/38 (5.3%)
Neutrophil count decreased	4/38 (10.5%)
Platelet count decreased	11/38 (28.9%)
Weight loss	3/38 (7.9%)
White blood cell decreased	4/38 (10.5%)
Metabolism and nutrition disorders
Anorexia	5/38 (13.2%)
Hypocalcemia	2/38 (5.3%)
Hypokalemia	2/38 (5.3%)
Hypomagnesemia	2/38 (5.3%)
Hyponatremia	2/38 (5.3%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	3/38 (7.9%)
Myalgia	2/38 (5.3%)
Nervous system disorders
Headache	4/38 (10.5%)
Peripheral motor neuropathy	2/38 (5.3%)
Peripheral sensory neuropathy	4/38 (10.5%)
Respiratory, thoracic and mediastinal disorders
Cough	3/38 (7.9%)
Epistaxis	3/38 (7.9%)
Skin and subcutaneous tissue disorders
Rash acneiform	4/38 (10.5%)
Rash maculo-papular	2/38 (5.3%)
Vascular disorders
Hypertension	2/38 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.