Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Small Cell Lung Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Pembrolizumab

Vaccines

Poly ICLC

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Interferons

* 4 cycles of standard of care (SOC) platinum doublet chemotherapy (investigator's choice)
* Pembrolizumab (200 mg every 3 weeks (Q3W) for 4 cycles while patient is receiving SOC chemo). Pembrolizumab may continue to be administered Q3W for a maximum of 35 total administrations
* All patients will begin the NEO-PV-01 vaccination at Week 12, 3 weeks following the 4th cycle of pembrolizumab / chemotherapy. At Week 12 (Cycle 5), NEO-PV-01 vaccinations will be administered in a prime-boost schedule with 5 priming vaccinations over a 3 week period followed by booster vaccinations at 1 month and 2 months after the last priming vaccination
* Up to 20 personalized vaccine peptides will be administered for each patient. Vaccine administration will occur on Days 1, 4, 8, 15 during Cycle 5 of pembrolizumab administration and Day 1 of Cycle 6 of pembrolizumab administration, on Day 8 during Cycle 7 of pembrolizumab administration, and on Day 15 during Cycle 8 of pembrolizumab administration

-Pembrolizumab will be given intravenously over the course of 30 minutes

-Generation of the vaccine is expected to take approximately 12 weeks

NEO-PV-01 vaccine

-Surgical or core needle biopsy of an accessible site for DNA and RNA sequencing, immunological analysis, and generation of NEO-PV-01 vaccine

Biopsy

-NEO-PV-01 is combined with the adjuvant poly-ICLC prior to administration.

-Peripheral blood mononuclear cells (PBMCs) for comprehensive immune system monitoring will be obtained from leukapheresis samples collected up to 7 days prior to initiation of NEO PV-01 vaccination and at 7 days (Week 20) following the first NEO-PV-01 booster vaccination.

Leukapheresis

-Blood samples (80 mL) for immune monitoring will be obtained prior to study treatment and at Weeks 6, 14, 16, 24, 36, 48, 63, 75, 87, and 99.

Peripheral blood samples

Ramaswamy Govindan, M.D.

Both metastatic squamous non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC) are incurable with current therapies, but due to mutations induced by cigarette smoke, typically express a large number of altered proteins that can be recognized as foreign by the immune system. This antigenicity is thought to explain the efficacy of pembrolizumab as either a first or second line treatment in this disease. For patients who receive chemotherapy plus immunotherapy as a first line therapy, there is sound rationale for combination treatment with immunotherapy and a therapeutic antitumor vaccine as a maintenance strategy. Regardless of PD-L1 expression in the tumor, monoclonal antibodies that block PD-1/PD-L1 interactions are effective second line therapies after chemotherapy in both NSCLC and SCLC. In addition, by targeting the immune system against tumor specific antigens using a peptide vaccine, the efficacy of pembrolizumab alone is expected to be enhanced, with an improved response rate and prolonged overall survival with no additional toxicity.

This pilot study will provide a preliminary test of the feasibility of generating a personalized, tumor neoantigen-specific therapeutic vaccine and the safety of combining it with checkpoint blockade immunotherapy.

Please note that this study originally opened with ID# 201707041 but was withdrawn due to change in standard of care chemotherapy. This study was revised and submitted as an amendment to the same IND but our IRB required it to be submitted as a new study and it received a new ID#.

Personalized Therapeutic Anti-tumor Vaccine With Pembrolizumab and Standard of Care Chemotherapy in Squamous Non-Small Cell Lung Cancer and Extensive Stage Small Cell Lung Cancer

Pilot Feasibility Study of the Combination of a Personalized Therapeutic Anti-tumor Vaccine With Pembrolizumab and Standard of Care Chemotherapy in Squamous Non-Small Cell Lung Cancer and Extensive Stage Small Cell Lung Cancer

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

--Percentage of participants who experience a complete or partial response

* Complete Response (CR): Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm
* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
* Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

-PFS is defined as the duration of time from start of personalized vaccine treatment (\~12 weeks after baseline) to time of progression or death, whichever occurs first.

Merck Sharp & Dohme LLC

Washington University School of Medicine

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Antirheumatic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Hormones

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

* MCS110 will be administered intravenously over 60 minutes (up to 120 minutes permitted) on a 28-day cycle. The dose of MCS110 given will depend on the dose level to which a given patient is enrolled.
* The standard neoadjuvant chemotherapy regimen of dose-dense doxorubicin/ cyclophosphamide followed by weekly paclitaxel consists of:

  * doxorubicin 60 mg/m\^2 IV Q2W during Weeks 1 through 8 (total of 4 doses)
  * cyclophosphamide 600 mg/m\^2 Q2W during Weeks 1 through 8 (total of 4 doses)
  * paclitaxel 80 mg/m\^2 IV QW during Weeks 9 through 20 (total of 12 doses)
* Surgery will be performed approximately 4-6 weeks after the end of the last cycle of treatment (Week 20-22). It is outside the scope of this study as part of each patient's standard of care. Both types of surgery (lumpectomy or mastectomy) are allowed. The decision on surgical approach and timing will be at the discretion of the treating surgeon.

-MCS110 is an IgG1/κ humanized monoclonal antibody directed against human macrophage colony stimulating factor

MCS110

-Time of enrollment and at time of surgery

Bone marrow aspirate

Tumor tissue

Leonel Hernandez-Aya, M.D.

In patients with locally advanced hormone receptor positive (HR+)/HER2- breast cancer, neoadjuvant chemotherapy produces a pathologic complete response rate (pCR) of only 9-15%, and late recurrences often occur despite neoadjuvant chemotherapy. Therefore, there is an unmet clinical need to improve the outcomes of these patients. Tumor-associated macrophages (TAM) infiltration leads to poor outcomes in breast cancer patients by promoting angiogenesis, activating epithelial-mesenchymal transition, degrading the extracellular matrix, and suppressing the anti-tumor immune response. Pre-clinical studies, as summarized above, have shown that the breast cancer immune microenvironment may be reprogrammed by targeting colony-stimulating factor-1 (CSF-1) to decrease TAM infiltration and increase CD8+ TIL infiltration, in order to foster antitumor immunity and improve response to therapy.

Here, the investigators propose a phase I dose-escalation study in patients with locally advanced HR+/HER2- breast cancer to determine the feasibility of adding MCS110, a CSF-1 inhibitor, to the standard neoadjuvant chemotherapy regimen of dose-dense doxorubicin, cyclophosphamide followed by paclitaxel. The investigators will also include a dose expansion cohort for preliminary efficacy analysis and correlative studies. The investigators propose that if they can decrease the TAM-induced immunosuppression and TAM-induced chemoresistance observed in breast cancer patients, then the patients' own immune system could find and destroy the dormant and resistant tumor cells, and combined with enhanced chemotherapy efficacy, the investigators will see durable remissions and long term cures.

MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer

Phase I Study of MCS110 Combined With Neoadjuvant Dose-Dense Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer

* The maximum tolerated dose (MTD) is defined as the dose level at which \<1 patients of a cohort (of 3 to 6 patients) experience dose-limiting toxicity during the first cycle.
* A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of CTCAE Grade ≥ 3 assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle of treatment with the combination treatment and meets any of the criteria outlined.

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

-Pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes. All eligible patients who have completed neoadjuvant therapy and have subsequently undergone surgery are included in the analysis of pCR.

-Residual invasive tumor size (RITS) is histopathologically assessed by the largest dimension of the dominant invasive tumor focus from the surgical specimen. In cases in which there was no residual invasive tumor, the RITS will be 0 mm. In cases in which multifocal pathology is present, the largest dimension of the residual invasive tumor focus will be recorded.

-Number of positive axillary lymph nodes is defined as number of resected lymph nodes with axillary nodal micrometastases (\>0.2-\<2 mm) or overt metastases (⩾2 mm).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Personalized Therapeutic Anti-tumor Vaccine With Pembrolizumab and Standard of Care Chemotherapy in Squamous Non-Small Cell Lung Cancer and Extensive Stage Small Cell Lung Cancer	NCT03166254	Non Small Cell ... NSCLC Non-small Cell ... Small Cell Lung...	Pembrolizumab NEO-PV-01 vacci... Biopsy Poly ICLC Leukapheresis Peripheral bloo...	18 Years -	Washington University School of Medicine
MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer	NCT03285607	Breast Cancer Cancer of Breas...	MCS110 Doxorubicin Cyclophosphamid... Paclitaxel Bone marrow asp... Peripheral bloo... Tumor tissue	18 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for peripheral blood samples