Clinical Trials Actively Recruiting

Primary Objective:

• To determine if ado-trastuzumab emtansine (T-DM1) shows better progression-free survival (PFS) when compared to docetaxel plus trastuzumab (TH) in recurrent and/or metastatic (R/M) HER2-positive salivary gland cancer (SGC) patients who have not previously received HER2 therapy for unresectable or recurrent and/or metastatic disease, as determined by local assessment.

Secondary Objectives:

• To compare the overall response rate (ORR) by RECIST v1.1 criteria between arms;
• To compare overall survival (OS) between arms;
• To compare toxicity using CTCAE v5.0 criteria between arms;
• To assess patient-reported toxicity, as measured by the PRO-CTCAE, between arms, and explore patient-reported symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the PRO-CTCAE.

Primary Objectives:

• Phase II: To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of progression-free survival (PFS).
• Phase III: To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of overall survival (OS).

Secondary Objectives:

• To further assess the efficacy of nivolumab compared with observation in terms of the relationship of baseline PD-L1 expression to clinical outcome.
• To evaluate the predictive value of HPV16 E6 and E7 DNA in saliva and plasma, at baseline, 12 weeks and 9 months after completion of radiation on PFS and OS in both arms of the study.
• To evaluate the tumor mutation burden by whole exome sequencing of the initial pretreatment tissue sample as well as samples obtained at the time of progression.
• To evaluate the association of 12 week post therapy FDG PET/CT with PFS and OS.
• To establish the prognostic value of SUVmax of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS).
• To correlate SUVmax of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive vs. negative).
• To correlate the post therapy (cisplatin + RT) FDG PET/CT with saliva or plasma levels of HPV DNA collected at the time of the standard 3 months PET/CT scan as well as 6 months later (i.e. 9 months post therapy) for both the observation and Nivolumab groups.
• To compare the PET based therapy response assessment (Hopkins criteria) to the RECIST 1.1 assessment at 12 week post chemoradiation therapy, for patients who have a PET/CT scan at 12 weeks.

Primary Objectives:

• To evaluate the feasibility of molecular characterization based on TMB for
  participant stratification, as assessed by the proportion of participants with less
  than or equal to a 21-day turnaround time for biopsy results in Stage I of the study.
• To evaluate the feasibility of molecular characterization based on TMB and GEP
  (for TIS) for stratification in the overall study (Stage I and Stage II).
• To evaluate the efficacy by overall response rate (ORR – defined as confirmed
  and unconfirmed partial responses plus complete responses) of cabozantinib plus
  nivolumab in each disease cohort, both across and within tumor biomarker
  subgroups.

Secondary Objectives:

• To assess the difference in ORR in each disease cohort between tumor marker
  subgroups separately for each disease cohort.
• To assess safety and tolerability of this treatment in these populations.
• To estimate disease control rate (DCR) in participants receiving cabozantinib plus
  nivolumab in each disease cohort, stratified by tumor biomarkers.
• To estimate progression-free survival (PFS) in participants receiving cabozantinib
  plus nivolumab in each disease cohort, stratified by tumor biomarkers.
• To estimate overall survival (OS) in participants receiving cabozantinib plus
  nivolumab in each disease cohort, stratified by tumor biomarkers.
• To assess the proportion of patients with assay failure, and the time from the date
  of tissue collection to molecular group determination at the end of Stage I.
• To assess turnaround time for TIS for at least 30 patients in Stage I to ensure that
  at least 75% have a turnaround time of <21 days. If TIS is not ready for real-time
  testing when 30 slots remain for Stage I, accrual will be paused until assay
  validation is complete

Primary Objective:

• To evaluate the disease-free survival (DFS) of patients with stage III-IV SCCHN and disruptive p53 mutations after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin.

Secondary Objectives:

• To evaluate the DFS of patients with stage III-IV SCCHN and non-disruptive p53 mutations after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin
• To evaluate the DFS of patients with stage III-IV SCCHN and p53 wild type after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin
• To evaluate toxicities of PORT alone or PORT with concurrent cisplatin.
• To evaluate p53 mutation as a predictive biomarker of survival benefit given post-operative concurrent radiation and cisplatin.
• To identify potential genomic alterations in addition to TP53 mutations that may be developed to a novel treatment approach.

Primary Objectives Phase II:

To determine if patient-reported neck and shoulder function and related quality of life (QOL) at 6 months after surgery using the Neck Dissection Impairment Index (NDII) is superior with Sentinel Lymph Node (SLN) biopsy compared to Elective Neck Dissection (END) for treatment of early-stage oral cavity squamous cell carcinoma (OCSCC) (cT1-2N0).

Primary Objectives Phase III:

• To determine if disease-free survival (DFS) is non-inferior with SLN biopsy compared to END for treatment of early-stage OCSCC (cT1-2N0).
• To determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using NDII is superior with SLN biopsy compared to END for treatment of early-stage OCSCC (cT1-2N0).

Secondary Objectives:

• To compare patterns of failure (local-regional relapse and distant metastasis) between surgical arms.
• To measure and compare overall survival (OS) between surgical arms.
• To measure and compare the toxicity of the two surgical arms.
• To measure longitudinal patient-reported neck and shoulder function and related QOL between surgical arms, using the following instruments:
• Neck Dissection Impairment Index (NDII)
• Abbreviated Disabilities of the Arm, Shoulder and Hand (QuickDASH)
• Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N)
• To assess the length of hospitalization, post-operative drain placement, and operative morbidity between arms.
• To estimate the negative predictive rate of FDG PET/CT for N0 neck in patients with T1 and T1-2 oral cavity squamous cell cancer (OCSCC) patients in the END arm.
• To assess nodal metastases rates between arms.
• To assess the pathologic false omission rate (FOR) in the SLN biopsy arm.
• To determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using the NDII is superior with the SLN biopsy compared to the END in low-risk patients.

Module A Monotherapy—dose escalation

Primary Objective:

• To investigate the safety and tolerability of EP0031 given as monotherapy

Secondary Objective:

• To characterize the PK of EP0031 given as monotherapy, after a single dose and at steady state after multiple dosing

Modules B and C Monotherapy—dose expansion

Primary Objective:

• To assess the efficacy of EP0031 given as monotherapy in patients with RET-altered tumours who have progressed following firstgeneration SRI therapy and in patients with RET-altered tumors with no prior SRI therapy (by RECIST v1.1)

Secondary Objectives:

• To investigate the safety and tolerability of EP0031 given as monotherapy
• To characterize the PK of EP0031 given as monotherapy

Primary Objectives:

• To evaluate the safety and tolerability of FT825 with or without cetuximab following CY/FLU or bendamustine
• To define the RP2D of FT825 with or without cetuximab following CY/FLU or bendamustine

Secondary Objectives:

• To evaluate the antitumor activity of FT825 with or without cetuximab following CY/FLU or bendamustine
• To characterize the PK of FT825 with or without cetuximab following CY/FLU or bendamustine

Primary Objectives:

• To evaluate the safety and tolerability of SGN-PDL1V in subjects with advanced solid tumors.
• To identify the maximum tolerated dose (MTD) of SGN-PDL1V in subjects with advanced solid tumors.
• To identify a recommended dose and schedule for SGN-PDL1V.

Secondary Objectives:

• To assess the antitumor activity of SGN-PDL1V.
• To assess the pharmacokinetics (PK) of SGN-PDL1V.
• To assess the immunogenicity of SGN-PDL1V.

Primary Objectives:

• To assess the safety and tolerability of AB598 in participants with advanced malignancies

Secondary Objectives:

• To describe the pharmacokinetic (PK) profile of AB598 in participants with advanced malignancies
• To assess the immunogenicity to AB598 in participants with advanced malignancies
• To assess the preliminary clinical activity of AB598 in patients with advanced malignancies

Dose Escalation (Monotherapy)

Primary Objectives:

• To evaluate safety and tolerability of MDNA11 administered in patients with advanced solid tumors
• To identify RDE and/or MTD of MDNA11.

Secondary Objectives:

• To assess anti-tumor activity of MDNA11
• To assess pharmacokinetic (PK) profile of MDNA11
• To assess immunogenicity of MDNA11
• To assess pharmacodynamic effects of MDNA11

Dose Expansion (Monotherapy and Combination Therapy)

Primary Objectives:

• To further evaluate safety and tolerability of MDNA11 (alone or in combination with pembrolizumab)
• To assess anti-tumor activity of MDNA11 (alone or in combination with pembrolizumab)

Secondary Objectives:

• To assess pharmacodynamic effects of MDNA11 (alone or in combination pembrolizumab) in peripheral blood
• To assess pharmacodynamic effects and immune response of MDNA11 (alone or in combination pembrolizumab) in tumor tissue
• To further assess PK profile of MDNA11
• To assess immunogenicity of MDNA11 (alone or in combination pembrolizumab)