Clinical Trials Actively Recruiting

Primary Objective:

• To compare overall survival (OS) between proton craniospinal irradiation (pCSI) and involved-field radiotherapy (IFRT) in patients with breast cancer or non-small cell lung cancer (NSCLC) leptomeningeal metastasis.

Secondary Objectives:

• To compare central nervous system progression-free survival (CNS PFS) between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.
• To compare time to CNS progression between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.
• To compare CNS PFS between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis, as evaluated by central review of imaging.
• To compare the rate of radiation-induced central nervous system necrosis between pCSI vs. IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.
• To characterize treatment-related adverse events using CTCAE v5.0.
• To compare patient-reported outcomes (Symptoms Severity subscale per MDASI-BT and MDASI-SP) in patients with breast cancer or non-small cell lung cancer leptomeningeal metastasis

Primary Objectives:

• To compare the overall survival in patients with stage II-IIIC inoperable nodepositive
  non-small cell lung cancer (NSCLC) after image guided, motion-managed
  conventional radiotherapy to the primary tumor and nodal metastases (Arm 1) or after
  image guided, motion-managed stereotactic body radiation therapy (SBRT) to the
  primary tumor followed by conventionally fractionated radiotherapy to nodal
  metastases (Arm 2) both given with concurrent platinum-based chemotherapy.
• To compare progression-free survival between the experimental arm (Arm 2) and
  control arm (Arm 1).

Secondary Objectives:

• To compare objective response rate (as defined by RECIST v 1.1) between the
  experimental arm and control arm
• To compare the rate of local control between the experimental arm and control arm
• To compare patterns of failure (primary, locoregional, or distant) between the
  experimental arm and control arm
• To compare changes in pulmonary function (FEV1 and DLCO assessed at
  randomization and at 6 and 12 months following completion of radiation therapy)
  between the experimental arm and control arm
• To compare changes in quality of life and patient-reported outcomes assessed from
  pre-treatment to 3 months following radiation therapy of each treatment arm
• To determine acute and late toxicity profiles of each treatment arm as measured by
  the CTCAEv5

Primary Objective

• Determine whether stereotactic radiosurgery (SRS) relative to whole brain radiotherapy with hippocampal avoidance (HA-WBRT) plus memantine for brain metastases from small cell lung cancer (SCLC) prevents cognitive function failure as measured by cognitive decline on a battery of tests: the Hopkins Verbal Learning Test – Revised (HVLT-R), Controled Oral Word Association (COWA) test, and the Trail Making Test (TMT).

Secondary Objectives

• Determine whether SRS relative to HA-WBRT plus memantine for brain metastases from SCLC preserves cognitive function as separately measured by the HVLT-R, COWA, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP).
• Assess perceived difficulties in cognitive abilities using PROMIS after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
• Assess symptom burden using the MD Anderson Symptom Inventory for brain tumor (MDASI-BT) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
• Compare cumulative incidence of intracranial disease progression after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
• Compare overall survival after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
• Compare cumulative incidence of neurologic death after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
• Compare the number of salvage procedures used to manage recurrent intracranial disease following SRS relative to HA-WBRT plus memantine for SCLC brain metastases.
• Compare adverse events between the treatment arms according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria.
• Compare the risk of developing cerebral necrosis between SRS and HA-WBRT plus memantine in patients receiving concurrent immunotherapy.

Primary Objective

Phase II:

• To compare investigator-assessed progression free survival (PFS) between atezolizumab plus radiotherapy and atezolizumab alone

Phase III:

• To compare overall survival (OS) between atezolizumab plus radiotherapy and atezolizumab alone

Secondary Objectives

• To assess the toxicity between the atezolizumab plus radiotherapy arm and the atezolizumab arm
• To assess the impact of adding radiotherapy on PFS and OS in patients with 1-3 visible tumors and >3 visible tumors
• To assess the impact of adding radiotherapy on PFS and OS in patients receiving consolidation radiotherapy to all visible disease (“complete consolidation”) and patients who do not receive consolidation radiation to all visible disease (“incomplete consolidation”)

Part 1: Dose Selection

Primary Objective:

• To evaluate investigator-assessed objective response (OR) of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion by dose level

Secondary Objectives:

• To evaluate investigator-assessed disease control (DC) of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion by dose level
• To evaluate investigator-assessed clinical benefit (CB) of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion by dose level
• To evaluate investigator-assessed duration of response (DOR) of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion by dose level
• To evaluate investigator-assessed progression-free survival (PFS) of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion by dose level
• To evaluate investigator-assessed time to objective response (TTOR) of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion by dose level
• To assess the safety and tolerability of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion by dose level
• Part 2 + Selected Dose from Part 1

Primary Objective:

• To evaluate OR of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion

Secondary Objectives:

• To evaluate investigator-assessed OR of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate DC of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate investigator-assessed DC of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate CB of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate investigator-assessed CB of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate PFS of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate investigator-assessed PFS of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate TTOR of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate investigator-assessed TTOR of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate DOR of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To evaluate investigator-assessed DOR of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To assess OS of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To assess the safety and tolerability of BMS-986504 in participants with advanced or metastatic NSCLC with homozygous MTAP deletion
• To assess the impact of disease symptoms and treatment on participant’s healthrelated quality-of-life in participants with advanced or metastatic NSCLC with homozygous MTAP deletion

Primary Objective

• To evaluate the pharmacokinetic (PK) profile of pralatrexate when administered to patients with various degrees of hepatic impairment

Secondary Objectives

• To evaluate the safety of pralatrexate when administered once weekly for 6 weeks of every 7-week treatment cycle
• To establish the dosing recommendations for pralatrexate administered once weekly for 6 weeks of every 7-week treatment cycle in patients with hepatic impairment

Primary Objective:

• To determine the recommended dose for Part 2 (RP2D) and to assess the efficacy of WSD0922-FU by assessment of ORR by RECIST v1.1.

Secondary Objectives:

• To further assess the efficacy of WSD0922-FU in terms of: - Progression Free Survival (PFS) - Duration of Response (DoR) - Disease Control Rate (DCR) - Change in Tumor Size - Overall Survival (OS)
• To assess the effect of WSD0922-FU on patients’ disease-related symptoms and health related quality of life (HRQoL).
• To characterize the PK of WSD0922-FU and metabolites in patients receiving WSD0922-FU.

Primary Objective:

Phase 1 dose escalation:

• To determine the safety and tolerability of TAK-188 administered in adult participants with locally advanced or metastatic solid tumors.

Phase 2 dose expansion:

• To assess the preliminary efficacy of TAK-188 in recurrent locally advanced or metastatic NSCLC, PD-L1 positive SCCHN, and gastroesophageal (esophageal, gastroesophageal junction, and gastric) adenocarcinoma post anti-PD-(L)1 therapy.

Secondary Objective:

Phase 1 dose escalation:

• To determine the RDE(s) of TAK-188.
• To characterize the PK of TAK-188.
• To evaluate the preliminary efficacy of TAK-188 in locally advanced or metastatic solid tumors.
• To evaluate the changes from baseline of Treg abundance, Teff abundance and/or the ratio of Teffs:Tregs within the TME in response to treatment with TAK-188.
• To assess the immunogenicity of TAK-188.

Phase 2 dose expansion:

• To further assess the preliminary efficacy of TAK-188 in recurrent locally advanced or metastatic NSCLC, PD-L1 positive SCCHN, and GEA post anti-PD-(L)1 therapy.
• To characterize the PK of TAK-188.
• To evaluate the changes from baseline of Treg abundance, Teff abundance, and/or the ratio of Teffs:Tregs within the TME in response to treatment with TAK-188.
• To assess the immunogenicity of TAK-188.

Safety Objective:

Phase 2 dose expansion:

• To determine the safety and tolerability of TAK-188 in participants with locally advanced or metastatic NSCLC, SCCHN, and GEA.

Primary Objectives:

Safety

• To assess the safety and tolerability of AZD5335 monotherapy and in combination with anti-cancer agents in participants with advanced solid tumors.

Secondary Objectives:

Efficacy

• To determine an effective dose to take forward into phase II (RP2D) for both AZD5335 monotherapy and in combination with anti-cancer agents.
• To assess the preliminary anti-tumor activity of AZD5335 as monotherapy and in combination with anti-cancer agents (second part not relevant for Module 1).

PK

• To characterize the PK of AZD5335 when given as monotherapy and in combination with anti-cancer agents

Immunogenicity

• To determine the immunogenicity of AZD5335.

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.