No prior immunotherapy for advanced/metastatic MCC
Have not received prior anti-cancer therapy for advanced or metastatic melanoma
Diagnosed with advanced or metastatic malignancy
For Part A dose confirmation: All participants must have histological evidence of advanced or metastatic soft tissue sarcoma or breast cancer. Breast cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
For Part B dose confirmation: All participants must have histological evidence of advanced or metastatic colon cancer or soft tissue sarcoma. Colon cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
For Part C dose confirmation: All participants must have histological evidence of advanced or metastatic breast cancer and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
For Part E dose confirmation: All participants must have histological evidence of locally advanced or metastatic triple negative breast cancer (TNBC) and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >2 lines of systemic treatment for advanced or metastatic TNBC.
Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC with tumor accessible for biopsy
Incurable advanced solid tumors that are no longer responding to conventional therapy or for which no effective therapy exists; at the RD of Part 1, an extension cohort up to 20 patients with metastatic breast cancer who are known to be BRCA mutation carriers will be enrolled.
During Phase 2, subjects with advanced cancer who have received at least one prior therapy or are treatment naive, depending on the specified tumor type.
Cohort 1: advanced breast cancer, ISH positive or IHC 3+.
Cohort 2: advanced breast cancer, ISH negative with IHC 2+.
Have advanced or metastatic cancer (solid tumors) and be an appropriate candidate for experimental therapy.
Part B2: Have advanced/metastatic cancer carrying activating mitogen-activated protein kinase (MAPK) pathway alteration
Parts A, A2 & B1: Participants must have pathological evidence of a diagnosis of advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate candidate for experimental therapy
Advanced myelofibrosis
Advanced measurable malignancy
Advanced Gastric Cancer
Patients must have pathologically confirmed advanced/metastatic cancer prior to enrollment.
Self-identified Black, African or African American women with proven diagnosis of advanced breast cancer (locoregionally recurrent or metastatic disease), either from the primary or a metastatic site
To be eligible for Cohort 5, patients must not have received any systemic therapy for advanced/metastatic disease
For the dose escalation phase, patients must have histologically confirmed metastatic solid tumor (metastatic or unresectable, locally advanced gastrointestinal [GI] cancers [e.g., esophageal, colorectal, pancreatic and others]), ovarian and breast cancers; the malignancy should be considered incurable using standard treatment; for the extension cohort (N=12) and for the expansion phase (N=45), patients with advanced breast cancer (N=15), advanced gastrointestinal cancer (N=15) and advanced ovarian (N=15) will be enrolled; all patients enrolled on the extension and expansion phase will be required to have measurable disease
Advanced myelofibrosis
Has a pathologically documented advanced/unresectable or metastatic breast cancer
All parts except Part B, Part E2, and Part E3 dose expansion: Must have diagnosis of cancer that is advanced or metastatic
Part E2 dose expansion: must have cancer that is advanced or metastatic and have prior documentation of a mutation of PIK3CA
Progressed after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer
Patient has confirmed HER2-negative advanced breast cancer (aBC)
Diagnosis of advanced stage or metastatic HER2-positive cancer with disease progressed after receiving at least one prior systemic therapy (immunohistochemistry or RT-PCR is used to determine HER2 positivity)
For Phase 1: Subjects who have advanced or metastatic disease as noted above that have received at least one prior therapy or have advanced or metastatic disease for which no curative treatment is available may be enrolled.
Phase 2: Subjects with advanced or metastatic endometrial cancer, gastric cancer (including stomach, esophageal, and GEJ), and SCCHN.
Inclusion Criteria:\n\n        Among other criteria, patients must meet all of the following conditions to be eligible for\n        the study:\n\n          1. Diagnosed with metastatic (i.e., cancer that has spread) TNBC\n\n               -  minimal or no expression of estrogen and progesterone receptors (ER/PR) <10% of\n                  cells positive by immunohistochemistry\n\n               -  HER 2 staining 0 or 1+ by IHC or copy number <4.0 signals/cell\n\n          2. Documented progression of disease based on radiographic, clinical or pathologic\n             assessment during or subsequent to the last anticancer regimen received.\n\n          3. Breast cancer tumor confirmed to express gpNMB. This will be determined by submitting\n             a tissue sample from the advanced (locally advanced/recurrent or metastatic) disease\n             setting to a central laboratory for analysis.\n\n          4. Received no more than two prior chemotherapy treatments for advanced (locally\n             advanced/recurrent or metastatic) breast cancer.\n\n          5. Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or\n             Doxil) if clinically indicated and a taxane (eg: Taxol).\n\n          6. ECOG performance status of 0 - 1.\n\n          7. Adequate bone marrow, liver and renal function.\n\n        Exclusion:\n\n        Among other criteria, patients who meet any of the following conditions are NOT eligible\n        for the study:\n\n          1. Progression/recurrence of breast cancer during or within 3 months of completion of\n             neoadjuvant or adjuvant chemotherapy.\n\n          2. Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are\n             moderate (Grade 2) or worse in severity.\n\n          3. Known brain metastases, unless previously treated and asymptomatic for 2 months and\n             not progressive in size or number for 2 months.\n\n          4. Significant cardiovascular disease.\n\n          5. Previously received capecitabine and discontinued due to progression or intolerance;\n             previously received CDX-011 or other MMAE containing agents.\n\n          6. Active systemic infection requiring treatment. Infection controlled by oral therapy\n             will not be exclusionary.\n\n          7. Chronic use of systemic corticosteroids.
For Part B: All participants must have a histological evidence of their advanced or metastatic cancer and prescreened alterations in a defined pathway.
For Part D: All participants must have histological evidence of advanced or metastatic cancer and prescreened alterations in a defined pathway.
Radiologic/objective evidence of breast cancer recurrence or progression while on or within 12 months of the end of adjuvant treatment with an AI, or progression while on or within 1 month of the end of prior AI treatment for locally advanced or metastatic breast cancer
Patients who received more than one chemotherapy line for advanced breast cancer.
newly diagnosed advanced/metastatic breast cancer at diagnosis that progressed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor)
Patients who received any prior hormonal anti-cancer therapy for advanced breast cancer, except for ? 14 days of tamoxifen or NSAI ± goserelin for advanced breast cancer prior to randomization.
Advanced measurable malignancy
Participants with radiologic/objective evidence of breast cancer recurrence or progression while on or within 6 months after the end of adjuvant treatment with an AI, or progression while on or within 1 month after the end of prior AI treatment for locally advanced or metastatic breast cancer
Advanced or metastatic cancer
Part D: Breast cancer that is advanced and/or metastatic
Part E: Melanoma that is advanced and/or metastatic
Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
Histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion may not be a candidate for curative surgery or radiation therapy). Successful vaccine manufacture has resulted from tissue/fluid obtained from the following major organ systems: digestive, endocrine, reproductive, respiratory, and urinary.Individuals manufactured under CL-PTL 105 (Phase II Ovarian) may be eligible for enrollment without advanced or metastatic disease.
Confirmed diagnosis of: \r\n* Postmenopausal advanced hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer after failure of treatment with letrozole or anastrozole\r\n* Progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic\r\n* Advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib
Initial diagnosis of advanced stage disease must have occurred ? 6 weeks prior to starting Cycle 1 Day 1. NOTE: The clock for this time interval starts with the date of last evaluation confirming advanced disease (either biopsy or imaging results).
Received prior treatment with capecitabine or fluoropyrimidine for advanced or metastatic disease
Previous systemic therapy for advanced or metastatic disease.
With advanced breast cancer whose disease was refractory to previous letrozole or anastrozole
Have advanced or metastatic cancer and be an appropriate candidate for experimental therapy.
Advanced cervical or endometrial cancer, T3/T4 lesions
Prior or concomitant treatment for advanced breast cancer.
Have advanced or metastatic cancer and be an appropriate candidate for experimental therapy.
Metastatic or advanced breast cancer that is evaluable OR metastatic or advanced breast cancer that is measurable for response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Histologically or cytologically confirmed: solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative treatment is no longer effective (Part 1); any type of advanced or refractory solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which standard curative treatment is no longer effective (Part 2); advanced or refractory squamous non-small cell lung cancer (Cohort A, Part 3), advanced or refractory small cell lung cancer (Cohort B, Part 3), advanced or refractory breast cancer (Cohort C, Part 3), any type of advanced or refractory solid malignancy (excluding lymphoma) ([consisting of one of the following: gastric, head and neck, lung adenocarcinoma, urothelial, glioblastoma multiforme (GBM), ovarian or prostate]) (Cohort D, Part 3), advanced or refractory non small cell lung cancer(Cohort E, Part 4), any type of advanced or refractory solid malignancy (consisting of one of the following: Breast, Urothelial, GBM, Ovarian, Head & Neck, Esophageal, Gastric, and Cholangiocarcinoma) (Cohort F, Part 4)
Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis. Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:
Patients with advanced cutaneous or subcutaneous in-transit or metastatic melanoma
Has received prior capecitabine treatment for advanced breast cancer
Diagnosis of an advanced solid tumor malignancy (advanced cancer) or lymphoma; in most situations, this would be a stage IV cancer; patients with a diagnosis of stage III cancer or lymphoma are eligible if cure is not possible or anticipated; clinical staging without pathological confirmation of advanced disease is allowed
Men and women with recurrent or advanced breast cancer
Key Inclusion Criteria\n\n        All Study Parts:\n\n          -  Diagnosis of cancer that has been histologically or cytologically confirmed\n\n          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1\n\n        Part A (1 of the following):\n\n          -  Ovarian cancer, triple-negative breast cancer, head and neck squamous cell cancer,\n             bladder cancer, metastatic colorectal cancer, pancreatic ductal adenocarcinoma, or\n             gastric cancer that is measurable or evaluable, nonmeasurable as defined by RECIST\n             v1.1 and meets 1 of the following criteria:\n\n               -  is refractory to standard of care\n\n               -  no standard therapy available\n\n               -  patient refuses standard therapy\n\n          -  Advanced, unresectable, or metastatic melanoma with or without prior treatment and\n             measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1\n\n          -  Advanced/metastatic PD-L1-positive NSCLC (defined as a tumor proportion score [TPS] ?\n             50%) with measurable or evaluable, non-measurable disease as defined by RECIST v1.1 (1\n             of the following):\n\n               -  1) No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic\n                  aberrations\n\n               -  2) Disease progression on or after platinum-containing chemotherapy;\n\n               -  3) If tumor has EGFR or ALK genomic aberrations, disease progression on an\n                  FDA-approved therapy for EGFR or ALK genomic tumor aberrations\n\n        Phase 2 (1 of the following):\n\n          -  Advanced/metastatic solid tumor with PD as defined by RECIST 1.1 or irRC on an\n             anti-PD-1- or anti-PD-L1-containing regimen as their most recent prior therapy\n\n          -  Advanced/metastatic epithelial ovarian cancer, peritoneal cancer or tubal cancer with\n             measurable disease as defined by RECIST 1.1, that had progressed within 6 months of\n             completing ? 4 cycles of platinum-based therapy\n\n          -  Advanced/metastatic PDA that is locally advanced, unresectable or metastatic with\n             measurable disease as defined by RECIST v1.1 in patients who have received at least\n             one prior line of systemic therapy for their disease\n\n        Key Exclusion Criteria\n\n          1. Prior treatment as follows:\n\n               -  Part A: an immune CPI (e.g., PD-1, PD-L1, or cytotoxic T-lymphocyte antigen 4\n                  [CTLA-4] inhibitor).\n\n             NOTE: For patients with melanoma, prior treatment with ipilimumab is allowed if it was\n             administered as adjuvant therapy and treatment was completed at least 3 months prior\n             to enrollment.\n\n               -  Phase 2:\n\n                    -  A CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor.\n\n                    -  prOVCA and PDA patients only: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4\n                       inhibitor)\n\n          2. Symptomatic brain metastasis at screening\n\n          3. Active autoimmune disease, documented history of autoimmune syndrome or disease, or a\n             chronic medical condition that requires chronic steroid therapy or immunosuppressive\n             medication\n\n          4. History of pneumonitis or interstitial lung disease\n\n          5. Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality\n             that may increase the risk associated with study participation or study drug\n             administration or that may interfere with the interpretation of study results and, in\n             the judgment of the Investigator, would make the patient an inappropriate candidate\n             for the study\n\n          6. Ocular melanoma
Advanced or metastatic breast cancer
(Patient participation) Diagnosis of advanced cancer
Advanced, incurable cancer
Patient with a diagnosis of advanced cancer (metastatic or recurrent incurable solid tumors excluding prostate cancer)
A new diagnosis (within 3 months) of advanced cancer and/or patients receiving ongoing care from a medical oncologist (solid tumors) or a new recurrence of the primary cancer in an advanced stage
A diagnosis of advanced cancer (defined as metastatic or recurrent) with fatigue >= 4/10 (0-10 scale) on the Edmonton Symptom Assessment Scale (ESAS)
Definition of advanced cancer includes those patients who have metastatic or refractory disease according to their treating oncologist
Diagnosis of an advanced solid tumor malignancy (advanced cancer) or lymphoma; in most situations, this would be a stage IV cancer; a patient with a diagnosis of stage III cancer or lymphoma is eligible if cure is not possible or anticipated; clinical staging without pathological confirmation of advanced disease is allowed
Subjects must have histologic documentation of advanced recurrent or metastatic cancer.
Diagnosis of advanced (metastatic or recurrent) lung, breast, colorectal, prostate, or gynecological (GYN), or other solid tumor cancer; the symptom cluster of pain, fatigue, and sleep disturbance is common in these patients
Unresectable advanced or metastatic ACC, non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor
No findings in the rectum of advanced adenoma, chronic inflammation, or cancer
Advanced periodontal disease (gum disease)
Subject has been diagnosed with an advanced solid malignancy; advanced solid malignancy is defined as loco regional or systemic metastatic disease of at least 1 cm in diameter; tumor types allowed include: triple negative breast, prostate, colorectal, gastric, ovarian, pancreatic, esophageal, soft tissue sarcoma, and head & neck cancer; subjects with primary or metastatic skin disease only are excluded from participation in this study
Confirmed diagnosis of advanced, refractory breast or prostate cancer that is evaluable by radiologic testing. Participants must have experienced tumor progression on or treatment intolerance to at least one prior therapy.
Oncologists who do not have enough patients with advanced cancer
Inclusion Criteria:\n\n        All subjects:\n\n          -  Pathologically confirmed diagnosis of solid tumors\n\n          -  Metastatic disease\n\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1\n\n          -  Adequate bone marrow, hepatic and renal function\n\n          -  Normal Electrocardiogram (ECG)\n\n          -  18 years of age or above\n\n          -  Able to understand and sign informed consent\n\n        Pilot study only:\n\n        - CRC, TNBC, ER/PR Breast Cancer, NSCLC, Pancreatic Cancer, Ovarian Cancer, Gastric Cancer,\n        Gastroesophageal Junction (GEJ) adenocarcinoma, Head and Neck Cancer\n\n        Expansion Phase Additional Criteria:\n\n          -  Locally advanced or metastatic breast cancer\n\n          -  Received at least one cytotoxic therapy in the locally advanced and metastatic setting\n\n          -  Received ? 5 prior lines of chemotherapy in the metastatic setting\n\n          -  Candidate for chemotherapy\n\n        Expansion Phase Cohort 3 additional inclusion criteria:\n\n          -  Breast cancer with active brain metastasis\n\n          -  Neurologically stable\n\n        Exclusion Criteria:\n\n          -  Active Central nervous system (CNS) metastasis (applies to pilot phase and expansion\n             phase cohort 1 and 2 only)\n\n          -  Clinically significant GI disorders\n\n          -  Prior irinotecan or bevacizumab therapy within last 6 months and for Expansion Phase\n             patients, have received any prior treatment with Topol inhibitor\n\n          -  Known hypersensitivity to MM-398 or ferumoxytol\n\n          -  Inability to undergo MRI\n\n          -  Active infection\n\n          -  Pregnant or breast feeding\n\n          -  Prior chemotherapy administered within 3 weeks, or within a time interval less than at\n             least 5 half-lives of the agent, whichever is longer, prior to the first scheduled day\n             of dosing in this study\n\n          -  Received radiation therapy in the last 14 days\n\n          -  Treated with parenteral iron in the previous 4 weeks
SCLC or PAC that is advanced or has spread to other parts of the body