Objective:

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.

Objective:

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

Objective:

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.

Objective:

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

Objective:

Dose Escalation

Primary Objective

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

Secondary Objectives

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

Dose Expansion

Primary Objective

• To characterize the safety and tolerability of AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies

Secondary Objectives

• To characterize the PK profile of AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies
• To assess the immunogenicity to AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies
• To assess the clinical activity of AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies

Objective:

Primary Objective:

• To evaluate the antitumor activity of disitamab vedotin in subjects with previously treated, locally-advanced unresectable or metastatic (LA/m) HER2 expressing solid tumors

Secondary Objectives:

• To evaluate the safety and tolerability profile of disitamab vedotin
• To assess other measures of antitumor activity of disitamab vedotin per investigator assessment by other clinically relevant measures
• To evaluate the pharmacokinetics (PK) of disitamab vedotin
• To evaluate the immunogenicity of disitamab vedotin

Objective:

Primary Objectives:

• To characterize the safety and tolerability of different dose levels of ZL-1218 when administered as a single agent and in combination with pembrolizumab (200 mg IV Q3 week), including dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of ZL-1218.

Secondary Objectives:

• To assess the preliminary efficacy of ZL-1218 when administered as a single agent and in combination with pembrolizumab.
• To characterize the pharmacokinetics (PK) of ZL-1218 as a single agent or in combination with pembrolizumab, after a single dose and multiple doses.
• To evaluate the immunogenicity of ZL-1218 as a single agent or in combination with pembrolizumab, after a single dose and multiple doses.

Objective:

Primary Objectives:

• To evaluate safety and tolerability of ALE.C04 as monotherapy and in combination with pembrolizumab (Phase I Dose Escalation)
• To establish RP2D for ALE.C04 in combination with pembrolizumab (Phase I RDEs)
• To assess anti-tumor activity of ALE.C04 monotherapy (Phase II)
• To establish RP2D of ALE.C04 monotherapy (Phase II)
• To compare anti-tumor efficacy of ALE.C04 in combination with pembrolizumab versus pembrolizumab monotherapy (Phase II)

Secondary Objectives:

• To assess the preliminary antitumor activity of ALE.C04 as monotherapy and in combination with pembrolizumab by evaluating tumor response (Phase I and Phase II)
• To characterize the PK of ALE.C04 following a single dose administration and at steady state after multiple dosing as monotherapy and in combination with pembrolizumab (Phase I and Phase II)
• To evaluate the immunogenicity of ALE.C04 as monotherapy and in combination with pembrolizumab (Phase I and Phase II)
• Patient Reported Outcomes (Phase II, randomized)

Objective:

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.

Objective:

Primary Objectives:

• To evaluate tolerability of xevinapant when added to weekly cisplatin-based CRT in LA SCCHN

Secondary Objectives:

• To characterize safety of xevinapant when added to weekly cisplatin-based CRT in LA SCCHN
• To evaluate clinical activity parameters using Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1
• To evaluate time to subsequent cancer treatments in participants treated with xevinapant when added to weekly cisplatin-based CRT in LA SCCHN