Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Neoplasm Metastasis

Melanoma

Sarcoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Germ Cells Tumors

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Analgesics

Cyclophosphamide

Vaccines

Immunomodulating Agents

Celecoxib

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

autologous tumor vaccine plus chemotherapy

5x 10\^7 autologous tumor cells emulsified in 0.5 mL ISCOMATRIX adjuvant will be administered IM every 4 weeks for 6 months

Epigenetically Modified Autologous Tumor

50 mg PO BID for 7 days prior to the first dose of vaccine and then on days 8 through 14, and 22 through 28 of each 4 week treatment cycle

400 mg PO BID for 7 days prior to the first dose of vaccine and then on days 1 through 28 of each 4 week vaccine cycle.

David S Schrump, M.D.

Background:

- A tumor cell vaccine is an experimental cancer treatment. Cancer cells are collected from a patient and then used to develop a vaccine. The vaccine will produce an immune system response to help destroy other cancer cells in the body. Researchers are studying ways to improve these tumor cell vaccines. One way is to add an adjuvant. An adjuvant is a substance that brings about a stronger immune system response. ISCOMATRIX is an adjuvant that has been used safely in other clinical studies. But it has not been studied with certain tumor cell vaccines. Researchers want to find out whether a tumor cell vaccine with ISCOMATRIX, given along with cancer drug treatment, is a safe and effective way to slow or prevent tumor growth after tumor removal surgery.

Objectives:

- To assess the safety and effectiveness of tumor cell vaccines given with ISCOMATRIX and drug therapy after tumor removal surgery.

Eligibility:

- People at least 18 years of age who have had tumor cell vaccines developed from cells taken from surgically removed tumors.

Design:

* Patients will be screened with a physical examination, medical history, blood and urine tests, and imaging studies.
* Patients will be treated with cyclophosphamide (once daily) and celecoxib (twice daily) for 7 days before the first vaccine dose.
* Patients will receive the tumor cell vaccine once a month for 6 months. They will continue to receive drug therapy throughout the vaccine treatment. Patients will be monitored with regular blood tests and imaging studies.
* After the first 6 months, patients who have an immune response to the vaccine will continue treatment with the vaccine and chemotherapy. They will also have regular blood tests and imaging studies. They will have this treatment for up to 24 months from the first vaccination or until they no longer have an immune response.
* Participants will have followup visits for up to 5 years after the first vaccination, or until the tumor returns.

Background:

Cancer-testis (CT) antigens (CTAs) have emerged as attractive targets for cancer immunotherapy. Whereas cancers of various histologies exhibit CTA expression, primary or vaccine-induced immune responses to these antigens appear uncommon in patients with these malignancies, possibly due to low-level, heterogeneous antigen expression, and inadequate vaccination strategies. Because numerous CT antigens can be induced in tumor cells by DNA demethylating agents and HDAC inhibitors, it is conceivable that vaccination of cancer patients with autologous tumor cells exposed to chromatin remodeling agents will enhance anti-tumor immunity in these individuals. In order to examine this issue, patients undergoing complete resection of sarcomas, melanomas, germ cell tumors and epithelial malignancies metastatic to the lungs, pleura or mediastinum will be vaccinated with autologous tumor cells exposed ex-vivo to decitabine and radiation following completion of appropriate combined modality therapy. Vaccines will be administered in conjunction with ISCOMATRIX adjuvant as well as metronomic oral cyclophosphamide (50 mg PO BID x 7d q 14d), and celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant CTAs as well as delayed type hypersensitivity to autologous epigenetically modified tumor cells will be assessed before and after vaccination.

Primary Objective:

-To assess the safety of an epigenetically modified autologous tumor cell vaccine administered with ISCOMATRIX adjuvant in combination with metronomic oral cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy.

Eligibility:

* Patients with histologically or cytologically proven or clinically evident sarcoma, melanoma, or epithelial malignancies metastatic to lungs, pleura or mediastinum who can be rendered no evidence of disease (NED) by metastasectomy.
* Patients must be 18 years or older with an ECOG performance status of 0 2, without evidence of unstable or decompensated myocardial disease. Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted; pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no immunosuppressive medications except inhaled corticosteroids at the time vaccination commences.
* Patients must have a platelet count greater than 100,000, an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of \<1.5 x upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2) at the time vaccination commences.

Design:

* Patients will undergo thoracic metastasectomy using standard of practice guidelines.
* Portions of the resected tumors will be transferred to the Thoracic Oncology Laboratory. Cells will be processed to establish a cancer cell line.
* Following recovery from surgery and appropriate adjuvant chemotherapy and/or radiation, patients will be vaccinated with epigenetically-modified autologous tumor cells periodically over 6 months in conjunction with metronomic oral cyclophosphamide and celecoxib.
* Systemic toxicities and delayed type hypersensitivity responses to autologous tumor cells and serologic responses to a variety of CT antigens will be assessed before and after vaccination.
* Patients will be followed with routine staging scans until disease recurrence.
* As the exact set of comparisons and analyses to be performed will be determined following completion of the trial, and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive.
* Approximately 80 patients will be accrued to this trial in order to obtain up to 20 evaluable patients.

Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal

Epigenetically-Modified Autologous Tumor Cell Vaccs and ISCOMATRIX(TM) Adjuvant With Metronomic Oral Cyclophosphamide and Celecoxib in Pts Undergoing Resection of Sarcomas, Melanomas, Germ Cell Tumors, or Epithelial Malignancies Metastatic to Lungs, Pleura or Mediastinum

National Cancer Institute (NCI)

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

tumor cell vaccine administered with chemotherapy

50 mg PO BID for 7 days prior to the first dose of vaccine and then on days 8 through 14, and 22 through 28 of each treatment cycle.

4 vaccines consisting of approximately 2.5E7 cells each will be delivered IM every 4 weeks for 6 months. If immune response is detected after first 6 vaccinations, 2 more may be given at 3 month intervals.

Allogenic tumor Cell Vaccine (K562)

400 mg PO BID for 7 days prior to the first dose of vaccine and then on days 1 through 28 of each vaccine cycle.

Background:

- Certain types of cancers, including sarcoma and melanoma, have specific antigens (protein molecules) on their surfaces. Research has shown that producing an immune reaction to these antigens may be able to keep tumors from growing by encouraging the immune system to destroy the tumor cells. By creating a vaccine that contains antigens similar to those found on the cancer cells, researchers hope to cause an immune reaction that targets the cancer cells. However, more research is needed to determine the safety and effectiveness of this type of vaccine treatment.

Objectives:

- To determine whether a tumor cell vaccine, given to individuals who have had surgery to remove malignant tumors from the chest, can cause an immune reaction that will prevent the tumors from coming back.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with cancer that has spread to the lungs, pleura, or mediastinum, and have recently had surgery to remove tumors in the chest.

Design:

* Participants will be screened with a physical examination and medical history, as well as blood tests and imaging studies.
* Participants will have the option to have leukapheresis to collect white blood cells for studies on how the body is responding to the vaccine. Participants who agree to have this procedure will have it before the start of treatment and after the sixth and eighth vaccines.
* Seven days before the first vaccine, participants will receive the chemotherapy drugs celecoxib and cyclophosphamide to take twice a day at home.
* Participants will receive the experimental vaccine as an injection in the thigh or arm, and may receive it in two shots depending on how many cells are in each vaccine. Participants will receive a diary to monitor medication doses and side effects, as well as additional cyclophosphamide and celecoxib to take at home as directed by the study.
* Participants will have one vaccine every month for 6 months, and will have regular blood tests and imaging studies. After the sixth vaccine, participants who have successfully responded to the treatment will have two additional vaccines given 3 months apart.
* After the eighth vaccine, participants will have followup visits every 3 months for 1 year and then every 6 months for up to 4 years....

Background:

During recent years, the cancer-testis (CT) antigens (CTA) have emerged as attractive targets for cancer immunotherapy. Whereas malignancies of diverse histologies express a variety of CTAs, immune responses to these antigens appear uncommon in cancer patients, possibly due to low-level, heterogeneous antigen expression, as well as immunosuppressive regulatory T cells. Conceivably, vaccination of cancer patients with allogeneic tumor cells expressing high levels of multiple CTAs in combination with depletion of T regulatory cells will induce broad immunity to these antigens. In order to examine this issue, patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to lungs, pleura or mediastinum will be vaccinated with irradiated K562 erythroleukemia cells expressing GM-CSF (K562-GM) following thoracic metastasectomy. Vaccines will be administered in conjunction with metronomic oral cyclophosphamide (50 mg PO BID x 7d q 14d), and celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant CTAs will be assessed before and after vaccination.

Primary Objectives:

-To assess the safety of K562-GM allogeneic tumor cell vaccines in combination with oral metronomic cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy.

Eligibility:

* Patients with histologically or cytologically proven sarcoma, melanoma, or epithelial malignancies metastatic to lungs, pleura or mediastinum who can be rendered no clinical evidence of active disease (NED).
* Patients must be 18 years or older with an ECOG performance status of 0 2, without evidence of unstable or decompensated myocardial disease. Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted; pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no immunosuppressive medications except inhaled corticosteroids at the time vaccination commences.
* Patients must have a platelet count greater than 100,000, an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of \<1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2) at the time vaccination commences.

Design:

* Following recovery from thoracic metastasectomy, patients with NED or MRD will be vaccinated via deep subcutaneous injection with 1x10(8) irradiated K562 GM-tumor cells periodically over 6 months.
* Vaccines will be administered in conjunction with metronomic oral cyclophosphamide and celecoxib.
* Systemic toxicities, and immunologic response to therapy will be recorded. Pre and post vaccination serologic responses to a standard panel of CT antigens as well as cell mediated responses to epigenetically-modified autologous EBV-transformed B and autologous tumor cells (if available) will be assessed before and after vaccination.
* Numbers/percentages and function of T regulatory cells in peripheral blood will be assessed before, during, and after vaccinations.
* Patients will be followed in the clinic with routine staging scans until disease recurrence.
* As the exact set of comparisons and analyses to be performed will be determined following completion of the trial, and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive.
* Approximately 25 patients will be accrued to this trial.

Tumor Cell Vaccine for Patients Undergoing Surgery for Sarcomas, Melanomas, Germ Cell Tumors, or Malignancies That Have Metastasized to the Lungs, Pleura, or Mediastinum

Adjuvant Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Sarcomas, Melanomas, Germ Cell Tumors, or Epithelial Malignancies Metastatic to Lungs, Pleura, or Mediastinum

Number and description of immunologic responses to a panel of CT antigens in vaccinated patients

Assessment of T regs in peripheral blood before and after initiation of CP/celecoxib treatment

Antiemetics

Gastrointestinal Agents

Antipyretics

Respiratory System Agents

Antibodies

Antibodies, Monoclonal

Dexamethasone

Acetaminophen

Glucocorticoids

Dexamethasone acetate

Histamine Antagonists

Histamine H1 Antagonists

Immunoglobulins

Immunoglobulin G

Mitogens

Immunoglobulins, Intravenous

Montelukast

Histamine H2 Antagonists

Phase 1a: Patients are administered a weekly dose of 1 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Phase 1a: Patients are administered a weekly dose of 2 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Phase 1a: Patients are administered a weekly dose of 4 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Phase 1a: Patients are administered a weekly dose of 6 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Phase 1a: Patients are administered a weekly dose of 9 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Phase 1a: Patients are administered a dose of 6 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Phase 1a: Patients are administered a dose of 12 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Phase 1a: Patients are administered a dose of 15 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen. One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.

Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Sym013

Jordan Berlin, MD

This is the first study to test Sym013 (Pan-HER) in humans. The primary purpose of this study is to see if Sym013 is safe and effective for patients with advanced epithelial malignancies without available therapeutic options.

This is an open-label, multicenter trial composed of 2 parts in which Sym013 will be evaluated when administered by intravenous infusion in patients with advanced epithelial malignancies without available therapeutic options.

Part 1 is a Phase 1a dose-escalation evaluating weekly (Q1W) and every second week (Q2W) schedules of administration in separate dose-escalation cohorts to determine the recommended phase 2 dose (RP2D) and regimen of Sym013.

Part 2 is a Phase 2a dose-expansion at the RP2D and regimen. Four (4) dose-expansion cohorts will be evaluated in this part of the trial and will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets. Patients will be entered, depending upon either a defined molecular profile or profiles, or their underlying malignancy, to 1 of 4 corresponding expansion cohorts: Cohort A, Cohort B, Cohort C, or Cohort D.

Sym013 (Pan-HER) in Patients With Advanced Epithelial Malignancies

An Open-label, Multicenter, Phase 1a/2a Trial Investigating the Safety, Tolerability and Antitumor Activity of Multiple Doses of Sym013, a mAb Mixture Targeting EGFR, HER2 and HER3, in Patients With Advanced Epithelial Malignancies

Assess the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym013 administration.

No data were collected for this Outcome Measures as Part 2 of the trial was never initiated.

No RP2D or regimen of Sym013 was determined as the trial was prematurely terminated

Serum sampling to assess the potential for anti-drug antibody (ADA) formation was not analyzed as the trial was prematurely terminated

Will be estimated using non-compartmental methods and actual time points.

Will be derived from observed data. End of infusion was defined as time zero (0)

Will be estimated using non-compartmental methods and actual time points

Symphogen A/S

Phase 1a: Patients are administered a weekly dose of 1 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

1 mg/kg Q1W

Phase 1a: Patients are administered a weekly dose of 2 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

2 mg/kg Q1W

Phase 1a: Patients are administered a weekly dose of 4 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

4 mg/kg Q1W

Phase 1a: Patients are administered a weekly dose of 6 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

6 mg/kg Q1W + Prophylaxis

Phase 1a: Patients are administered a weekly dose of 9 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

9 mg/kg Q1W + Prophylaxis

Phase 1a: Patients are administered a dose of 6 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

6 mg/kg Q2W

Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

9 mg/kg Q2W

Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

9 mg/kg Q2W + Prophylaxis

Phase 1a: Patients are administered a dose of 12 mg/kg of Sym013 + premedication every second until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

12 mg/kg Q2W + Prophylaxis

Phase 1a: Patients are administered a dose of 15 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

15 mg/kg Q2W + Prophylaxis

Phase 1a: Patients are administered a dose of 12 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Body Mass Index (BMI)

Medical Director

Pts 84001-007 (9mg/kg Q2W) and 84002-01 (12 mg/kg +P Q2W) did not complete C1 and hence is not considered eligible for DLT assessments.

Part 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients.

Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen. One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 2a Dose-Expansion Cohort A

Phase 2a Dose-Expansion Cohort B

Phase 2a Dose-Expansion Cohort C

Phase 2a Dose-Expansion Cohort D

The outcome measure was not analyzed, because the study was stopped during Part 1 of the study before initiating Part 2 of the study for business reasons. No data were collected in Part 2

Part 2: Evaluate the Antitumor Effect of Sym013 When Administered at the RP2D and Regimen to Patients.

Phase 1a: Patients are administered a weekly dose of 1 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a weekly dose of 2 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a weekly dose of 4 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a weekly dose of 6 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a weekly dose of 9 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a dose of 6 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a dose of 12 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

Phase 1a: Patients are administered a dose of 15 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

No data were collected for this Outcome Measure for Parts 1 and 2

Part 1: Determine the RP2D and Regimen of Sym013.

Parts 1 and 2: Evaluate the Immunogenicity of Sym013.

Hu1277, 1st dose (1st PK profile), AUC

Hu1565, 1st dose (1st PK profile), AUC

Hu4384, 1st dose (1st PK profile), AUC

Hu4517, 1st dose (1st PK profile), AUC

Hu5038, 1st dose (1st PK profile), AUC

Hu5082, 1st dose (1st PK profile), AUC

Hu1277, 3rd/4th dose (2nd PK profile), AUC

Hu1565, 3rd/4th dose (2nd PK profile), AUC

Hu4384, 3rd/4th dose (2nd PK profile), AUC

Hu4517, 3rd/4th dose (2nd PK profile), AUC

Hu5038, 3rd/4th dose (2nd PK profile), AUC

Hu5082, 3rd/4th dose (2nd PK profile), AUC

Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 (+ premedication) every second week until unacceptable toxicity, progressive disease, termination of the trial or the patient decision to withdraw.

Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

Sym013: Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

9 mg/kg Q2W and 9 mg/kg Q2W + Prophylaxis

No patients in the 15 mg/kg Q2W + Prophylaxis group proceeded to the 3rd dose Not all patients completed both PK profiles; thus lower patient number in 2nd PK profile than in 1st profile

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal	NCT01341496	Sarcoma Melanoma Epithelial Mali... Pleural Maligna...	Epigenetically ... Cyclophosphamid... Celecoxib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal	NCT01341496	Sarcoma Melanoma Epithelial Mali... Pleural Maligna...	Epigenetically ... Cyclophosphamid... Celecoxib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Tumor Cell Vaccine for Patients Undergoing Surgery for Sarcomas, Melanomas, Germ Cell Tumors, or Malignancies That Have Metastasized to the Lungs, Pleura, or Mediastinum	NCT01313429	Sarcoma Melanoma Epithelial Mali... Pleural Maligna...	Cyclophosphamid... Allogenic tumor... Celecoxib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Tumor Cell Vaccine for Patients Undergoing Surgery for Sarcomas, Melanomas, Germ Cell Tumors, or Malignancies That Have Metastasized to the Lungs, Pleura, or Mediastinum	NCT01313429	Sarcoma Melanoma Epithelial Mali... Pleural Maligna...	Cyclophosphamid... Allogenic tumor... Celecoxib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Sym013 (Pan-HER) in Patients With Advanced Epithelial Malignancies	NCT02906670	Oncology	Sym013	18 Years -	Symphogen A/S

Spots Global Cancer Trial Database for epithelial malignancies