This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

T-DM1 and Tucatinib Compared With T-DM1 Alone in Preventing Relapses in People With High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04457596
Recruitment Status : Recruiting
First Posted : July 7, 2020
Last Update Posted : April 9, 2024
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Seagen Inc.
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief Summary:
This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in preventing breast cancer from coming back (relapsing) in patients with high risk, HER2 positive breast cancer. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors, and delivers DM1 to kill them. Tucatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving T-DM1 and tucatinib may work better in preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared to T-DM1 alone.

Condition or disease Intervention/treatment Phase
Anatomic Stage IA Breast Cancer AJCC v8 Anatomic Stage II Breast Cancer AJCC v8 Anatomic Stage IIA Breast Cancer AJCC v8 Anatomic Stage IIB Breast Cancer AJCC v8 Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IIIA Breast Cancer AJCC v8 Anatomic Stage IIIB Breast Cancer AJCC v8 Anatomic Stage IIIC Breast Cancer AJCC v8 HER2 Positive Breast Carcinoma Invasive Breast Carcinoma Multifocal Breast Carcinoma Prognostic Stage I Breast Cancer AJCC v8 Prognostic Stage IA Breast Cancer AJCC v8 Prognostic Stage IB Breast Cancer AJCC v8 Prognostic Stage II Breast Cancer AJCC v8 Prognostic Stage IIA Breast Cancer AJCC v8 Prognostic Stage IIB Breast Cancer AJCC v8 Prognostic Stage III Breast Cancer AJCC v8 Prognostic Stage IIIA Breast Cancer AJCC v8 Prognostic Stage IIIB Breast Cancer AJCC v8 Prognostic Stage IIIC Breast Cancer AJCC v8 Synchronous Bilateral Breast Carcinoma Biological: Trastuzumab Emtansine Drug: Placebo Administration Drug: Tucatinib Other: Questionnaire Administration Other: Quality-of-Life Assessment Phase 3

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine if the invasive disease-free survival (iDFS) with T-DM1 and tucatinib is superior to the iDFS in the control arm (T-DM1 + placebo) when administered to high risk patients with HER2-positive breast cancer and residual disease after neoadjuvant HER2-directed therapy.

SECONDARY OBJECTIVES:

I. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) improves the following:

Ia. Breast cancer free survival (BCFS). Ib. Distant recurrence-free survival (DRFS). Ic. Brain metastases-free survival (BMFS). Id. Overall survival (OS). II. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) reduces the incidence of brain metastases.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive T-DM1 intravenously (IV) over 30-90 minutes on day 1 and placebo orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive T-DM1 IV over 30-90 minutes on day 1 and tucatinib PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 6 months for 10 years.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1031 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The CompassHER2 Trials (Comprehensive Use of Pathologic Response Assessment to Optimize Therapy in HER2-Positive Breast Cancer) CompassHER2 Residual Disease (RD), a Double-Blinded, Phase III Randomized Trial of T-DM1 Compared With T-DM1 and Tucatinib
Actual Study Start Date : January 6, 2021
Estimated Primary Completion Date : January 2028
Estimated Study Completion Date : May 2035


Arm Intervention/treatment
Active Comparator: Arm I (trastuzumab emtansine, placebo)
Patients receive T-DM1 IV over 30-90 minutes on day 1 and placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Biological: Trastuzumab Emtansine
Given IV

Drug: Placebo Administration
Given PO

Other: Questionnaire Administration
Ancillary studies

Other: Quality-of-Life Assessment
Ancillary studies

Experimental: Arm II (trastuzumab emtansine, tucatinib)
Patients receive T-DM1 IV over 30-90 minutes on day 1 and tucatinib PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Biological: Trastuzumab Emtansine
Given IV

Drug: Tucatinib
Given PO

Other: Questionnaire Administration
Ancillary studies

Other: Quality-of-Life Assessment
Ancillary studies




Primary Outcome Measures :
  1. Modified invasive disease-free survival (iDFS) [ Time Frame: From randomization to one of the following events: invasive local, regional or distant recurrence, invasive contralateral breast cancer or death from any cause, assessed up to 10 years ]
    A Kaplan-Meier method will be used to estimate the survival curves and a stratified log-rank test will be used to compare the invasive disease-free survival (iDFS) of the two arms. A stratified Cox model will be used to estimate the hazard ratio. If there appears to be clinically significant imbalances of baseline variables between the treatment arms, a secondary analysis of the primary endpoint will use stratified Cox model to compare the treatment effects that include the variables that are deemed imbalanced between the arms as adjusting variables. The randomization stratification variables will be the stratified variables in the model.


Secondary Outcome Measures :
  1. Unmodified invasive disease-free survival (iDFS) [ Time Frame: Up to 10 years ]
    Will be defined as the time from randomization to one of the following events: invasive local, regional or distant recurrence, invasive contralateral breast cancer secondary primary invasive cancer (other than basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix), or death from any cause, assessed up to 10 years. A Kaplan-Meier method will be used to estimate the survival curves and a stratified log-rank test will be used to compare the iDFS of the two arms. A stratified Cox model will be used to estimate the hazard ratio.

  2. Breast cancer-free survival [ Time Frame: From randomization to invasive local, regional, or distant recurrence, or invasive contralateral breast cancer, assessed up to 10 years ]
    Will be summarized with Kaplan-Meier curves and compared between the arms using a stratified log-rank test and stratified Cox model. If there are clinically significant imbalances in baseline characteristics between the treatment arms, a second analysis will be done using a stratified Cox model with the variables that are imbalance added as adjusting variables.

  3. Distant recurrence-free survival [ Time Frame: From randomization to the first incidence of distant recurrence, assessed up to 10 years ]
    Will be summarized with Kaplan-Meier curves and compared between the arms using a stratified log-rank test and stratified Cox model. If there are clinically significant imbalances in baseline characteristics between the treatment arms, a second analysis will be done using a stratified Cox model with the variables that are imbalance added as adjusting variables.

  4. Brain metastases-free survival [ Time Frame: From randomization to documentation of involvement of the central nervous system by metastatic cancer including parenchymal brain and spinal cord metastases as well as leptomeningeal carcinomatosis, assessed up to 10 years ]
    Will be summarized with Kaplan-Meier curves and compared between the arms using a stratified log-rank test and stratified Cox model. If there are clinically significant imbalances in baseline characteristics between the treatment arms, a second analysis will be done using a stratified Cox model with the variables that are imbalance added as adjusting variables.

  5. Overall survival [ Time Frame: From randomization until death from any cause, assessed up to 10 years ]
    Will be summarized with Kaplan-Meier curves and compared between the arms using a stratified log-rank test and stratified Cox model. If there are clinically significant imbalances in baseline characteristics between the treatment arms, a second analysis will be done using a stratified Cox model with the variables that are imbalance added as adjusting variables.

  6. Incidence of brain metastases [ Time Frame: Up to 10 years ]
    An incident of brain metastases is documentation of involvement of the central nervous system by metastatic cancer including parenchymal brain and spinal cord metastases as well as leptomeningeal carcinomatosis. The cumulative incidence of brain metastases will be determined as the crude cumulative incidence as well as with incidence with competing risks where the competing event is death.


Other Outcome Measures:
  1. Quality of life [ Time Frame: Up to 8 cycles of treatment (each cycle is 21 days) ]
    Will be assessed by the Functional Assessment of Cancer Therapy (FACT)-Breast Cancer (B) Trial Outcome Index questionnaire. The mixed model will compare the cycle 9 day 1 and cycle 14 day 1 time points between randomized arms. In addition to a randomized arm covariate, the model will include a randomized arm-by-time interaction term and will use the planned cycle of assessment as the categorical time value. Unstructured covariance will initially be used, though alternative covariance structures will be investigated with the final covariance structure selected based on minimization of the Akaike information criterion. A contrast will be used to compare mean change from baseline at cycle 9 day 1 between arms. If the two-sided 95% confidence interval excludes a difference of 5 favoring the trastuzumab emtansine (T-DM1) + placebo arm, then non-inferiority will be concluded.

  2. Quality of life [ Time Frame: Up to 13 cycles of treatment (each cycle is 21 days) ]
    Will be assessed by the Functional Assessment of Cancer Therapy (FACT)-Breast Cancer (B) Trial Outcome Index questionnaire. The mixed model will compare the mean change from baseline at cycle 14 day 1 between arms. If the two-sided 95% confidence interval excludes a difference of 5 favoring the T-DM1 + placebo arm, then non-inferiority will be concluded at this time point.



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.


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

Inclusion Criteria:

  • HER2-positive status will be based on pretreatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) according to current American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines. Central testing is not required

    * Known hormone receptor (HR) status as defined by ASCO/CAP guidelines (based on pretreatment biopsy material). Hormone receptor positive status can be determined by either known positive estrogen receptor (ER) or known positive progesterone receptor (PR) status; hormone receptor negative status must be determined by both known negative ER and known negative PR

  • Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0 tumors are not eligible at initial breast cancer diagnosis are not eligible)
  • Patients with residual HR-negative, HER2 positive (+) disease in the breast and/or lymph nodes per the surgical pathology report are eligible; however, patients with HR+ HER2+ cancers must have node-positive residual disease per the surgical pathology report in order to qualify for the study. The presence of residual invasive disease in the breast is not mandatory for these patients
  • Patients with weakly ER-positive (1-10%) breast cancer (based on the pretreatment core biopsy) are eligible even if they have node-negative disease per the surgical pathology report
  • The residual disease tissue (breast and/or lymph nodes) is not required to be HER2-positive, as eligibility for NCI-2020-03770 (A011801) is based on a positive HER2 status at the time of the initial breast cancer diagnosis

    * Note: The presence of micrometastases in lymph nodes after preoperative therapy counts as residual disease, whereas the presence of isolated tumor cells does not

  • Patients with synchronous bilateral invasive disease are eligible provided both lesions were confirmed to be HER2-positive, and at least one of the lesions meets the criteria outlined above. Multifocal disease is allowed, as long as the largest biopsied breast tumor was HER2-positive
  • Patients must have received neoadjuvant chemotherapy with one of the following regimens: docetaxel/trastuzumab/pertuzumab (THP), paclitaxel/methotrexate/cisplatin (TMP), doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab (AC-TH(P)); docetaxel/carboplatin/trastuzumab/pertuzumab (TCH(P)); fluorouracil/doxorubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FAC-TH(P)), or fluorouracil/epirubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FEC-TH(P)). Note: apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is acceptable
  • Prior receipt of T-DM1 in the neoadjuvant setting is not allowed.

    • Prior treatment must have consisted of >= 6 cycles of chemotherapy and HER2-directed therapy, with a total duration of >= 12 weeks, including at least 9 weeks of preoperative taxane and trastuzumab with or without pertuzumab (or Food and Drug Administration [FDA]-approved biosimilars). Patients who have received at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also eligible if they received >= 6 cycles of systemic therapy prior to enrollment. Note: Patients who complete at least nine of a planned twelve doses of weekly paclitaxel, or three of a planned four doses of docetaxel, but discontinue prematurely due to toxicity are eligible. Patients receiving dose-dense chemotherapy regimens are also eligible. Prior use of nab-paclitaxel (Abraxane) instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is also allowed.
    • Patients who received neoadjuvant systemic therapy which included experimental HER2-targeted therapy/therapies are potentially eligible, as long as the investigational agent was not a HER2-targeted antibody-drug conjugate (e.g. T-DM1, DS-8201a [trastuzumab deruxtecan]) or a HER2 targeted tyrosine kinase inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).
  • Patients may have received =< 1 cycles of T-DM1 in the adjuvant setting. Note: These patients will be randomized to receive a further 14 cycles of T-DM1 and tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been administered =< 5 weeks prior to registration

    * Note: Both of the following two criteria need to be met for the patient to be eligible for this study

    • An interval of no more than 12 weeks between the completion date of the last definitive treatment (e.g. postoperative chemotherapy or radiation, or if neither given, breast surgical date) and the date of registration. Concurrent radiation therapy is permitted while receiving study treatment
    • Patients must be registered on study within =< 180 days of the date of the most recent definitive breast cancer surgery (not including reconstructive surgery)
  • All systemic chemotherapy should have been completed preoperatively unless participating in EA1181 (CompassHER2 pathologic complete response [pCR]) or the BIG DECRESCENDO Trial (which is very similar to CompassHER2 pCR in terms of study design, drugs, and eligibility). However, patients who received 4 cycles of neoadjuvant THP off study can receive a further 2-4 cycles of chemotherapy postoperatively to meet eligibility for A011801. Patients who participated in EA1181 or MA41 and proceeded to surgery immediately after the de-escalated trial regimen must receive postoperative chemotherapy to complete a total of >= 6 cycles of systemic treatment prior to enrollment on A011801, as outlined above (e.g. 4 cycles pre-operatively, and 2 cycles post-operatively). The postoperative chemotherapy regimen prescribed is at the discretion of the treating oncologist (i.e. 2-4 cycles AC or THP, other). Continuation of trastuzumab + pertuzumab (HP) pre- or post-operatively as maintenance therapy (while awaiting a surgical date or an official pathology report) is allowed for all study participants
  • Toxicities related to prior systemic treatment should have resolved or be at baseline, apart from alopecia and peripheral neuropathy =< grade 1
  • Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as follows:

    • Breast surgery: total mastectomy with no gross residual disease at the margin of resection, or breast-conserving surgery with histologically negative margins of excision
    • For patients who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection
    • Lymph node surgery ** The axilla needs to be evaluated with either sentinel node biopsy or axillary lymph node dissection. If patients have a sentinel lymph node biopsy and sentinel nodes are negative, no further axillary treatment is necessary. If patients have isolated tumor cells (ITCs) in the setting of residual breast disease, at least one of the following is required: axillary lymph node dissection (ALND) or planned nodal irradiation. If patients have micro- or macro-metastatic nodal disease, ALND and planned nodal irradiation are required. Of note, co-enrollment on Alliance A011202 is not allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Hemoglobin >= 8 g/dL (Note: packed red blood cells [PRBC] transfusion is not permitted to achieve eligibility)
  • Platelet count >= 100,000/mm^3
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Total bilirubin =< 1.0 x upper limit of normal (ULN) or direct bilirubin within the institutional normal range for patients with Gilbert's syndrome
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Screening left ventricular ejection fraction (LVEF) >= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute percentage points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55% after completion of neoadjuvant chemotherapy. Note: LVEF assessment may be repeated once up to 3 weeks following the initial screening assessment to assess eligibility

Exclusion Criteria:

  • No adjuvant treatment with any anti-cancer investigational drug within 28 days prior to registration
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to registration is required
  • Patients with known active and/or untreated hepatitis B or hepatitis C or chronic liver disease are ineligible. Patients with a diagnosis of hepatitis B or C that has been treated and cleared and normal liver function are eligible to participate in the study if the other eligibility parameters are met
  • Stage IV (metastatic) breast cancer
  • History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of registration
  • Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the surgical pathology report
  • Evidence of recurrent disease following preoperative therapy and surgery
  • Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
  • History of exposure to the following cumulative doses of anthracyclines: doxorubicin > 240 mg/m^2; epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m^2. For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
  • Cardiopulmonary dysfunction as defined by any of the following:

    • History of National Cancer Institute (NCI) CTCAE version (v) 5.0 grade >= 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria class >= II
    • Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease
    • High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular block (AV)-block (second degree AV-block type 2 [Mobitz 2] or third degree AV-block)
    • Significant symptoms (grade >= 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy
    • History of a decrease in left ventricular ejection fraction (LVEF) to < 40% with prior trastuzumab treatment (e.g., during preoperative therapy)
    • Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Current severe, uncontrolled systemic disease
  • Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to registration or anticipation of the need for major surgery during the course of study treatment
  • History of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
  • Peripheral neuropathy of any etiology that exceeds grade 1
  • Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol
  • Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to registration is prohibited.

    • Please note that use of sensitive CYP3A substrates should be avoided two weeks before registration and during study treatment. Additionally, CYP3A4 or CYP2C8 inducers are prohibited as concomitant medications within 5 days following discontinuation of tucatinib treatment. Patients who require medications that are known to be sensitive substrates of CYP3A4 with a narrow therapeutic window should be excluded.

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): NCT04457596


Contacts
Layout table for location contacts
Contact: Ciara C. O'Sullivan, MB, BCh, BAO 507-293-0526 osullivan.ciara@mayo.edu

Locations
Show Show 1154 study locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Seagen Inc.
Investigators
Layout table for investigator information
Study Chair: Ciara C. O'Sullivan, MB, BCh, BAO Mayo Clinic
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT04457596    
Other Study ID Numbers: A011801
NCI-2020-03770 ( Registry Identifier: NCI Clinical Trial Reporting Program )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: April 9, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Trastuzumab
Ado-Trastuzumab Emtansine
Maytansine
Tucatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunotoxins
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors