Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Skin and Connective Tissue Diseases

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Rare Diseases

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Laryngeal Diseases

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

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Nevus

Nevi and Melanomas

Skin Neoplasms

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Neoplasms

Esophageal Diseases

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

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Otorhinolaryngologic Diseases

Stomach Cancer

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Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

RAPA-201 cells will be administered at a target flat dose of 400 x 10\^6 cells per infusion.

Autologous Rapamycin-Resistant Th1/Tc1 Cells

RAPA-201 Rapamycin Resistant T Cells

Carboplatin + Paclitaxel Regimen (CP Regimen)

Chemotherapy Prior to RAPA-201 Therapy

Daniel Fowler, M.D.

Jennifer Sunga - Regulatory Affairs Associate

Chelsea McCabe, CCRP

Martin Gutierrez, M.D.

The therapy of solid tumors has been revolutionized by immune therapy, in particular, approaches that activate immune T cells in a polyclonal manner through blockade of checkpoint pathways such as PD-1 by administration of monoclonal antibodies. In this study, the investigators will evaluate the adoptive transfer of RAPA-201 cells, which are checkpoint-deficient polyclonal T cells that represent an analogous yet distinct immune therapy treatment platform for solid tumors.

RAPA-201 is a second-generation immunotherapy product consisting of reprogrammed autologous CD4+ and CD8+ T cells of Th1/Tc1 cytokine phenotype. First-generation RAPA-101, which was bred for resistance to the mTOR inhibitor rapamycin, demonstrated clear anti-tumor effects in multiple myeloma patients without any product-related adverse events. Second-generation RAPA-201, which have acquired resistance to the mTOR inhibitor temsirolimus, are manufactured ex vivo from peripheral blood mononuclear cells collected from solid tumor patients using a steady-state apheresis. RAPA-201 is also being evaluated for the therapy of relapsed, refractory multiple myeloma and was granted Fast Track Status by the FDA for this indication. The novel RAPA-201 manufacturing platform, which incorporates both an mTOR inhibitor (temsirolimus) and an anti-cancer Th1/Tc1 polarizing agent (IFN-alpha) generates polyclonal T cells with five key characteristics:

1. Th1/Tc1: polarization to anti-cancer Th1 and Tc1 subsets, with commensurate down-regulation of immune suppressive Th2 and regulatory T (TREG) subsets;
2. T Central Memory: expression of a T central memory (TCM) phenotype, which promotes T cell engraftment and persistence for prolonged anti-tumor effects;
3. Temsirolimus-Resistance: acquisition of temsirolimus-resistance, which translates into a multi-faceted anti-apoptotic phenotype that improves T cell fitness in the stringent conditions of the tumor microenvironment;
4. T Cell Quiescence: reduced T cell activation, as evidence by reduced expression of the IL-2 receptor CD25, which reduces T cell-mediated cytokine toxicities such as cytokine-release syndrome (CRS) that limit other forms of T cell therapy; and
5. Reduced Checkpoints: multiple checkpoint inhibitory receptors are markedly reduced on RAPA-201 cells (including but not limited to PD-1, CTLA4, TIM-3, LAG3, and LAIR1), which increases T cell immunity in the checkpoint-replete, immune suppressive tumor microenvironment.

This is a Simon 2-stage, non-randomized, open label, multi-site, phase I/II trial of RAPA-201 T immune cell therapy in patients with advanced metastatic, recurrent, and unresectable solid tumors that have recurred or relapsed after prior immune therapy. Patients must have tumor relapse after at least one prior line of therapy and must have refractory status to the most recent regimen, which must include an anti-PD-(L)1 monoclonal antibody. Furthermore, accrual is limited to solid tumor disease types potentially amenable to standard-of-care salvage chemotherapy consisting of the carboplatin + paclitaxel (CP) regimen that will be utilized for host conditioning prior to RAPA-201 therapy. Importantly, carboplatin and paclitaxel are "immunogenic" chemotherapy agents whereby the resultant cancer cell death mechanism is favorable for generation of anti-tumor immune T cell responses. Thus, the CP regimen that this protocol incorporates is intended to directly control tumor progression and indirectly promote anti-tumor T cell immunity. The CP regimen is considered standard-of-care therapy for the following tumor types, which will be focused upon on this RAPA-201 protocol: small cell and non-small cell lung cancer; breast cancer (triple-negative sub-type or relapse after ovarian ablation/suppression); gastric cancer (esophageal and esophageal-gastric-junction adenocarcinoma; gastric adenocarcinoma; esophageal squamous cell carcinoma); head and neck cancer (squamous cell carcinoma of oral cavity, larynx, nasopharynx, and other sites); carcinoma of unknown primary; bladder cancer; and malignant melanoma.

Protocol therapy consists of six cycles of standard-of-care chemotherapy (carboplatin + paclitaxel (CP) regimen) administered every 28 days (chemotherapy administered on cycles day 1, 8, and 15). RAPA-201 cells will be administered at a target flat dose of 400 X 10\^6 cells per infusion on day 3 of cycles 2 through 6.

A sample size of up to 22 patients was selected to determine whether RAPA-201 therapy, when used in combination with the CP regimen, represents an active regimen in solid tumors that are resistant to anti-PD(L)-1 checkpoint inhibitor therapy, as defined by a response rate (≥ PR) consistent with a rate of 35%. The first stage of protocol accrual will consist of n=10 patients; to advance to the second protocol accrual stage, RAPA-201 therapy must result in a tumor response (≥ PR) in at least 2 out of the 10 initial patients.

The therapy of solid tumors has been revolutionized by immune therapy, in particular, approaches that activate immune T cells in a polyclonal manner through blockade of checkpoint pathways such as PD-1 by administration of monoclonal antibodies. In this study, the investigators will evaluate the adoptive transfer of a reprogrammed T cell population termed RAPA-201 cells, which are checkpoint-deficient polyclonal T cells that represent an analogous yet distinct treatment platform for solid tumor immune therapy.

RAPA-201 is a second-generation T cell immunotherapy product that is comprised of autologous CD4+ and CD8+ T cells of Th1/Tc1 cytokine phenotype. The first-generation RAPA-101 product, which was bred for resistance to the mTOR inhibitor rapamycin and developed for therapy of multiple myeloma, demonstrated clear anti-tumor effects without any product-related adverse events. The second-generation RAPA-201 cells, which have acquired resistance to the mTOR inhibitor temsirolimus, are manufactured ex vivo from peripheral blood mononuclear cells collected from solid tumor patients using a steady-state apheresis. RAPA-201 cells are also being evaluated for the therapy of relapsed, refractory multiple myeloma and was granted Fast Track Status by the FDA for this indication. The novel method of RAPA-201 manufacturing, which incorporates both an mTOR inhibitor (temsirolimus) and an anti-cancer Th1/Tc1 polarizing agent (IFN-alpha) generates a polyclonal T cell population with the following five key characteristics:

1. Th1/Tc1: polarization to the anti-cancer Th1 and Tc1 subsets, with commensurate down-regulation of immune suppressive Th2 and regulatory T (TREG) subsets;
2. T Central Memory: expression of a T central memory (TCM) phenotype, which promotes T cell engraftment and persistence necessary for prolonged anti-tumor effects;
3. Temsirolimus-Resistance: acquisition of temsirolimus-resistance, which translates into a multi-faceted anti-apoptotic phenotype that improves T cell fitness in the stringent conditions of the tumor microenvironment;
4. T Cell Quiescence: reduced T cell activation, as evidence by reduced expression of the IL-2 receptor CD25, which reduces the chance of T cell-mediated cytokine toxicities such as cytokine-release syndrome (CRS) that limit other forms of T cell therapy; and
5. Reduced Checkpoints: multiple checkpoint inhibitory receptors are markedly reduced on RAPA-201 cells (including but not limited to PD-1, CTLA4, TIM-3, LAG3, and LAIR1), which increases T cell immunity in the checkpoint-replete, immune suppressive tumor microenvironment.

This is a multi-site phase I/II study evaluating RAPA-201 cells in up to 22 patients with relapsed solid tumors who have disease progression after anti-PD1 pathway monoclonal antibody therapy. The study will evaluate adoptive T cell therapy using autologous rapamycin-resistant Th1/Tc1 cells (RAPA-201) in the context of a standard-of-care chemotherapy regimen comprised of carboplatin plus paclitaxel (CP Regimen). The study will only accrue patients with solid tumor types that support use of the CP Regimen as a salvage therapy. Importantly, carboplatin and paclitaxel are considered "immunogenic" chemotherapy whereby the resultant cancer cell death mechanism is favorable for the generation of anti-tumor immune T cell responses. Therefore, the CP regimen that this protocol incorporates is intended to both directly control tumor progression and indirectly promote anti-tumor T cell immunity. The CP regimen is considered standard-of-care therapy for the following tumor types, which will therefore be focused upon on this RAPA-201 protocol: small cell and non-small cell lung cancer; breast cancer (triple-negative sub-type or relapse after ovarian ablation/suppression); gastric cancer (esophageal and esophageal-gastric-junction adenocarcinoma; gastric adenocarcinoma; esophageal squamous cell carcinoma); head and neck cancer (squamous cell carcinoma of oral cavity, larynx, nasopharynx, and other sites); carcinoma of unknown primary; bladder cancer; and malignant melanoma.

To be eligible for the protocol, a subject will be required to have a circulating absolute lymphocyte count (ALC) of ≥ 300 cells per microliter. This parameter will help ensure that a sufficient number of autologous RAPA-201 cells can be manufactured from a steady-state apheresis product. Once the apheresis product has been received at the manufacturing site, the subject can initiate the first cycle of the CP Regimen, which will be administered over a 28-day interval.

Within 10 days after positive determination of study eligibility (and subject enrollment), two key actions will occur: (1) T cells will be collected by steady-state apheresis and sent to the manufacturing site at Rapa Therapeutics; (2) and the patient will start Cycle 1 of the CP Regimen (with a window of up to 7 calendar days to begin).

The Carboplatin-Paclitaxel (CP) regimen will be given alone for Cycle 1 and in combination with RAPA-201 cells for Cycles 2-6. After the completion of the treatment portion of the study, the subject will enter the follow-up component that will last for 6 months.

Cycle 1 of the CP Regimen will be a 28-day cycle, which will allow for time to manufacture the RAPA-201 cell product. According to standard-of-care practice, the carboplatin and paclitaxel will be administered on days 1, 8, and 15 of each cycle. Each cycle, beginning with Cycle 1, may be delayed or extended for up to four weeks, if needed for various reasons, including: logistical considerations, resolution of adverse events, or if there is a delay in RAPA-201 manufacturing. Requests for using additional time between cycles, other than the visit windows specified in the Schedule of Events, should be approved by the Medical Monitor.

Cycles 2-6 will also be 28-day cycles but will include both the CP Regimen plus the infusion of RAPA-201 cells at a target flat dose of 400 X 10\^6 cells per infusion.

A sample size of up to 22 patients was selected to determine whether RAPA-201 therapy, when used in combination with the CP regimen, represents an active regimen in solid tumors that are resistant to anti-PD(L)-1 checkpoint inhibitor therapy, as defined by achieving a response rate (≥ PR) consistent with a rate of 35%. The first stage of protocol accrual will consist of n=10 patients; to advance to the second stage of protocol accrual, RAPA-201 therapy must result in a tumor response (≥ PR) in at least 2 out of the 10 initial patients.

Simon 2-stage, non-randomized, open label, multi-site, phase I/II trial

RAPA-201 Therapy of Solid Tumors

Phase I/II Trial of Autologous Rapamycin-Resistant Th1/Tc1 (RAPA-201) Cell Therapy of PD-(L)1 Resistant Solid Tumors

To characterize the phenotype of immune T cell reconstitution, as defined by peripheral blood T cell count, which will be determined by flow cytometry using the CD3+ marker. CD3+ T cell count will be compared pre-treatment (at study entry) and at one-year after study start.

To determine the safety of RAPA-201 cell therapy when used in combination with a carboplatin plus paclitaxel (CP) standard-of-care chemotherapy regimen. Specifically, the treatment will be determined to be safe if the following parameters are met: (Metric #1) using the metric of "unresolved grade 3 toxicity attributable to the RAPA-201 cell therapy": for positive determination of safety, this metric must occur in 3 or fewer patients out of the initial 10 patients; (Metric #2) using the metric of "grade 4 non-hematologic toxicity that is probably attributable to RAPA-201 cell therapy": for positive determination of safety, this metric must occur in 1 or fewer patients out of the initial 10 patients; and (Metric #3) using the metric of "grade 5 toxicity that is probably attributable to RAPA-201 cell therapy": for positive determination of safety, this metric must occur in 1 or few patients out of the initial 10 patients.

To determine the overall RECISTv1.1 criteria response rate (partial response or better) of autologous RAPA-201 cells and standard-of-care chemotherapy (carboplatin + paclitaxel) in patients with solid tumors resistant to PD-(L)1.

To characterize the effect of therapy on solid tumor disease control, as measured by progression free survival (PFS) and overall survival (OS).

To evaluate effect of therapy on quality of life (QOL) using the Short Form-36 Survey.

Rapa Therapeutics LLC

Symptoms and General Pathology

Neoplasm Metastasis

Mouth Neoplasms

Oral Cancer

Tegafur

Antimetabolites

Eligible patient will be given maintenance tegafur-uracil for one year.

Dose of tegafur-uracil will be based on patient's body surface area (BSA):

* BSA \< 1.5 m2: tegafur-uracil 300 mg/day (1 capsule three times a day)
* BSA ≥ 1.5 m2: tegafur-uracil 400 mg/day (2 capsules twice a day) Tegafur-uracil will be started after patient has complete the adjuvant radiotherapy and been enrolled into the study.

tegafur-uracil

Hung-Ming Wang, M.D.

Chia-Hsun Hsieh, M.D.

Primary Objective:

To determine the 2-year distant failure rate of maintenance tegafur-uracil in patients with squamous cell carcinoma of oral cavity with extracapsular spreading of lymph nodes.

Secondary Objectives:

* To determine the 2-year locoregional failure rate.
* To evaluate the 2-year overall survival (OS) rate.
* To evaluate the 2-year progression-free survival (PFS) rate.
* To assess the safety profiles.

The primary endpoint will be 2-years distant failure rate which will be estimated by Kaplan-Meier method with two-sided 95% confidence interval.

The secondary endpoints are described as follows:

* 2-year locoregional failure rate, 2-year PFS rate and 2-year OS rate will be estimated by Kaplan-Meier method with two-sided 95% confidence interval.
* Safety profile: adverse events will be summarized by CTCAE. Safety parameters will only be analyzed on the safety analysis set and be presented in frequency tabulation.

Determination of sample size:

The estimated 2-year distant failure rate for squamous cell carcinoma of oral cavity with extracapsular spreading of lymph nodes is 26%. The 2-year distant failure rate of maintenance treatment with tegafur-uracil in this study is expected to be 13%. Using One Proportional Test with one-sided alpha 0.05 and power 80%, the sample size of 56 subjects will test an effect size of 13% (i.e. 26% vs.13%). With expected dropout rate of 20%, the sample size would be 68 subjects.

Patients with resected squamous cell carcinoma of oral cavity harboring extracapsular spreading of lymph node s/p adjuvant chemoradiotherapy

Maintenance Tegafur-uracil in Resected Oral Cavity Cancer With ECS+

A Phase II Study of Maintenance Tegafur-uracil in Patients With Squamous Cell Carcinoma of Oral Cavity With Extracapsular Spreading of Lymph Nodes

the 2-year distant failure rate calculated from the date of surgery will be measured

the 2-year locoregional failure rate calculated from the date of surgery will be measured.

the 2-year overall survival rate calculated from the date of surgery will be measured

the 2-year progression-free survival rate calculated from the date of surgery will be measured.

Incidence of Treatment-Emergent Adverse Events will be measured by NCI-CTCAE version 4.0

Chang Gung Memorial Hospital

Mouth Diseases

Lip and Oral Cavity Cancer

Cisplatin

Preoperative chemotherapy with concurrent radiotherapy followed by definitive surgery

Three weekly concurrent chemotherapy with cisplatin 100 mg /m2

Neoadjuvant chemotherapy

Preoperative radiotherapy over 5 weeks- Dose 180-200cgys per day/ total 4500 cgys

Neoadjuvant radiotherapy

Resection and reconstruction of mandibular/maxillary segment with prefabricated fibular graft

Resection and reconstruction

Sanjay Deshmukh, MS

Oral cancer is the single largest cancer in males in India. 90-95% cases of oral cancer are Squamous cell carcinomas and many of them present at late stages (T3 and above). Treatment of OSCC includes single modality surgery, radiotherapy, or combinations of these modalities with or without systemic therapy. For unresectable cases, radiotherapy and/or chemotherapy is the treatment modality. Efficacy of neoadjuvant chemoradiotherapy for resectable stage IV tumors (late stage) needs to be evaluated to assess its benefit before surgery.

This study will assess the benefit of preoperative adjuvant chemoradiotherapy in patients with an Stage IVa oral squamous cell carcinoma (OSCC). The study population will consist of patients who have not been treated previously. Patients satisfying the inclusion-exclusion criteria will be included in the study after obtaining a valid, written and informed consent. After reviewing the histopathological report, the patients will be treated as per the study protocol. The patients will be under regular follow-up with 3 monthly intervals for a period of one year and 6 monthly period in the following years. At each follow-up, patients will be evaluated clinically for evidence of locoregional tumor recurrence. The locoregional recurrence-free survival will be calculated based on the difference between the date of inclusion and the date of biopsy-proven recurrence. We will also record the overall survival, parameters like trismus, osteonecrosis and xerostomia. Quality of life will be assessed at a regular interval of 1 year using the University of Washington Quality of Life Questionnaire (UW-QOL v.4)

Study protocol:

1. Preoperative radiotherapy over 5 weeks- Dose 180-200cgys per day/ total 4500 cgys
2. Three weekly concurrent chemotherapy with cisplatin 100 mg /m2
3. Initial surgery in leg for Prefabrication of fibula - 2 weeks after starting of radiotherapy treatment. Delay is required for planning of implant position in the fibula.
4. Definitive surgical procedure with reconstruction by prefabricated flap, 6 weeks post radiotherapy.

Adjuvant ChemoRadiotherapy Prior to Surgery in Stage IVa Oral Cancers

Assessing Efficacy of Neoadjuvant Chemoradiotherapy as a Treatment Plan for Patients With Stage IVa Oral Cancer.

Individual patient data for all primary and secondary outcomes will be made available.

This will be deduced from pathological response in terms of complete and partial response. Complete response is defined as no invasive and no in situ residuals present in the surgical specimen. Partial response defined as at least a 30% reduction in the size of the lesion in the surgical specimen.

Disease-free survival will be calculated as the time interval (months) between primary treatment and the first recurrence (whether local, regional or distant).

Overall Survival will be calculated as the time interval (months) between primary treatment and death.

Patient reported quality of life will be assessed at a regular interval of 1 year using the University of Washington Quality of Life Questionnaire (UW-QOL v.4). The minimum score is 0 which is indicative of worse outcome while 100 is the maximum score and indicative of better outcome. Various parameters including chewing, pain, swallowing, saliva, appearance etc. are included in the questionnaire. Average score for each parameter with standard deviation will be reported.

Tata Capital Limited

Grant Medical Foundation Ruby hall Clinic

Indrayani Hospital and Cancer Institute

Surgical Oncologist

Tubulin Modulators

Antimitotic Agents

Induction phase:

Chemotherapy based on carboplatin 6 AUC (area under the curve) + paclitaxel 75 mg/m2 carboplatin 6 AUC 30-minute infusion on D: 1 (maximum carboplatin dose is 700 mg) paclitaxel 75 mg/m2 1-hour infusion on D: 1, 8, 15

Radiotherapy:

D:1 - 2 x 0,5 Gy (first dose up to one hour after the end of the carboplatin infusion, second dose 3 to 6 hours later), D:2 - 2 x 0,5 Gy (interval between doses not less than 3 hours), D:8 and D:15 - 2 x 0,5 Gy (first dose up to one hour after the end of the chemotherapeutic infusion, second dose 3 to 6 hours later).

Chemotherapy based on carboplatin 6 AUC + paclitaxel 75 mg/m2.

Radiotherapy:

D:1 - 2 x 0,5 Gy (first dose up to one hour after the end of the carboplatin infusion, second dose 3 to 6 hours later), D:2 - 2 x 0,5 Gy (interval between doses not less than 3 hours), D:8 and D:15 - 2 x 0,5 Gy (first dose up to one hour after the end of the chemotherapeutic infusion, second dose 3 to 6 hours later).

Chemotherapy (carboplatin+paclitaxel) with concomitant low dose ionizing radiotherapy

Tomasz Rutkowski, MD PhD

Agnieszka Pietruszka, MD

Krzysztof Składowski, MD PhD

Non-commercial clinical study to assess:

1. efficacy of iCHRTL in patients with advanced squamous cell carcinoma of oral cavity, pharynx carcinoma, larynx carcinoma or paranasal sinus carcinoma.
2. tolerability of iCHRTL in patients with advanced squamous cell carcinoma of oral cavity, pharynx carcinoma, larynx carcinoma or paranasal sinus carcinoma.
3. molecular and biochemical effect of low doses of ionizing radiation.

40 patients with squamous cell carcinoma of oral cavity, pharynx, larynx or paranasal sinuses in stage III or IV, previously not treated for this reason and eligible for induction chemotherapy.

Study treatment:

Induction phase:

Chemotherapy based on carboplatin 6 area under the curve (AUC) + paclitaxel 75 mg/m2 carboplatin 6 AUC 30-minute infusion on D: 1 (maximum carboplatin dose is 700 mg) paclitaxel 75 mg/m2 1-hour infusion on D: 1, 8, 15

Radiotherapy:

D:1 - 2 x 0,5 Gy (first dose up to one hour after the end of the carboplatin infusion, second dose 3 to 6 hours later), D:2 - 2 x 0,5 Gy (interval between doses not less than 3 hours), D:8 and D:15 - 2 x 0,5 Gy (first dose up to one hour after the end of the chemotherapeutic infusion, second dose 3 to 6 hours later).

2 cycles of induction treatment are planned. Interval between the last day of cycle I and the first day of cycle II is 7 days. After 2 weeks from second cycle Positron emission tomography (PET) and Magnetic Resonance (MR), medical case conference and qualification to further treatment: Radiotherapy (RT), Chemo-radiotherapy (CHRT) or other, depending on the medical decision.

Planned based on the optimal technique for a particular clinical case preferred: Intensity Modulated Radiation Therapy (IMRT). Preparation of IMRT plan will be based on computed tomography (CT) scans. Early tolerance of radiotherapy will be assessed for local reaction. At least once every 7 days.

Interventional, open, allocation to concomitant chemotherapy and low-dose ionizing radiotherapy

Induction Treatment in SCC of the Head and Neck Region - Concomitant Chemotherapy and Low-dose Radiotherapy

Induction Treatment in Patients With Squamous Cell Carcinoma (SCC) of the Head and Neck Region Consisting Concomitant Chemotherapy and Low-dose Ionizing Radiotherapy

Rate of local lesions complete response (CR) +partial response (PR)+stable disease (SD)

Rate of death within time from treatment start to 1 year

Rate of death within time from treatment start to 3 years

Medical Research Agency, Poland

Maria Sklodowska-Curie National Research Institute of Oncology

Two pastilles (100 mg) taken three times a day (i.e. before meal time).

APG-157

Marilene B Wang, MD

Elizabeth Franzmann, MD

The purpose of this clinical research study is to study safety and efficacy of orally administered APG-157 as the neoadjuvant/induction therapy in newly diagnosed, locally advanced patients with Head \& Neck Cancer of oral cavity and/or oropharynx.

The study hypothesis is that neoadjuvant use of APG-157 will reduce the tumor burden prior to any definitive therapy to improve the outcomes over current standard of care.

The patient will receive neoadjuvant therapy (APG-157) during the period between initial diagnosis and time of definitive treatment. APG-157 is an orally administered drug in a form of pastille (soft lozenge) taken three times a day. It dissolves in the mouth. After the neoadjuvant treatment, the patient undergoes surgery or any other definitive therapy and/or postoperative radiotherapy as determined by the patient's doctor. Duration of treatment is four weeks that may be extended up to six weeks by mutual consent of the patients and the investigators.

Objectives:

1. To conduct Phase 2A to determine how tumor size, tumor tissue biomarkers, and the cancer stem cell markers, in head and neck squamous cell cancer patients are affected by the administration APG-157 pastilles using imaging and other clinical measurements.
2. To determine the degrees of response of each patient to APG-157 (considering patient's diagnosis/staging and local treatment) using proposed primary, secondary and exploratory endpoints.
3. The results from this study will be used to finalize the design of subsequent Phase 2B study (single arm for specific patient population and local treatment) to demonstrate statistically significant efficacy outcomes.

Safety and Efficacy of APG-157 in Head and Neck Cancer

Phase 2 Study to Evaluate the Safety and Efficacy of APG-157 as Neoadjuvant/Induction Therapy for Patients With Head and Neck Squamous Cell Cancer (HNSCC) of the Oral Cavity and/or Oropharynx

Change in Tumor Size from Baseline to end of dosing using MRI with or without contrast and PET/CT imaging.

Change in Immunohistochemistry profile (including the levels of tumor infiltrating lymphocytes TILs) of tumor biopsy from baseline to end of dosing.

Change in cytokine levels (IL-1β , TNF-α, IL-8) and oral microbiome (phyla and genus level changes in microbial composition using 16s RNA sequencing) in saliva from baseline to end of dosing.

Change in cell-free RNA biomarkers in blood and saliva from baseline to end of dosing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
RAPA-201 Therapy of Solid Tumors	NCT05144698	Solid Tumor Breast Cancer Small Cell and ... Triple Negative... Gastric Cancer Esophageal Aden... Gastric Junctio... Esophageal Squa... Head and Neck C... Squamous Cell C... Squamous Cell C... Squamous Cell C... Squamous Cell C... Carcinoma of Un... Bladder Cancer Malignant Melan...	RAPA-201 Rapamy... Chemotherapy Pr...	18 Years -	Rapa Therapeutics LLC
Maintenance Tegafur-uracil in Resected Oral Cavity Cancer With ECS+	NCT03121313	Squamous Cell C...	tegafur-uracil	20 Years - 70 Years	Chang Gung Memorial Hospital
Adjuvant ChemoRadiotherapy Prior to Surgery in Stage IVa Oral Cancers	NCT03923998	Squamous Cell C...	Neoadjuvant che... Neoadjuvant rad... Resection and r...	18 Years - 70 Years	Indrayani Hospital and Cancer Institute
Maintenance Tegafur-uracil in Resected Oral Cavity Cancer With ECS+	NCT03121313	Squamous Cell C...	tegafur-uracil	20 Years - 70 Years	Chang Gung Memorial Hospital
Induction Treatment in SCC of the Head and Neck Region - Concomitant Chemotherapy and Low-dose Radiotherapy	NCT05992610	Squamous Cell C... Pharynx Carcino... Larynx Carcinom... Paranasal Sinus...	Chemotherapy (c...	18 Years -	Maria Sklodowska-Curie National Research Institute of Oncology
Safety and Efficacy of APG-157 in Head and Neck Cancer	NCT05312710	Head and Neck C... Squamous Cell C... Squamous Cell C...	APG-157	18 Years -	Aveta Biomics, Inc.

Spots Global Cancer Trial Database for squamous cell carcinoma of oral cavity