Clinical Trials Actively Recruiting

Primary Objective:

• To evaluate the efficacy of NVL-655 compared to alectinib in patients with treatment-naïve ALK-positive advanced NSCLC

Secondary Objectives:

• To assess additional measures of efficacy of NVL-655 compared to alectinib in patients with treatment-naïve ALK-positive advanced NSCLC
• To evaluate the safety and tolerability of NVL-655 compared to alectinib
• To evaluate and compare patient-reported measures of health-related quality of life (QoL), lung cancer symptoms, patient functioning, and side effects of treatment

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:

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.

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”)

Phase I (dose escalation)

Primary Objectives:

• To identify the MTD and/or RP2D of ANV600 single agent and in combination with pembrolizumab

Secondary Objectives:

• To characterize the PK of ANV600 single agent and in combination with pembrolizumab after single dose and repeated dosing
• To evaluate the prevalence and incidence of immunogenicity of ANV600
• To describe the anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab

Phase II

Primary Objectives:

• To assess the anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab

Secondary Objectives:

• To assess the anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab
• To assess the safety and tolerability ANV600 single agent and in combination with pembrolizumab for each cohort and in the overall study population
• To characterize the PK of ANV600 single agent and in combination with pembrolizumab after single dose and repeated dosing
• To evaluate the prevalence and incidence of immunogenicity of ANV600

Primary Objectives:

• Evaluate SGR-3515 safety, tolerability, dose-limiting toxicities (DLTs) in participants with advanced solid tumors
• Identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended phase 2 dose (RP2D) and recommended schedule (RP2S) of SGR-3515

Secondary Objectives:

• Evaluate SGR-3515 PK in participants with advanced solid tumors
• Evaluate SGR-3515 preliminary anti-tumor activity in participants with advanced solid tumors as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or the applicable disease specific criteria

Primary Objectives:

Phase 1

• To identify potential OBRD and dosing regimens of MBRC-101
• To establish the MTD of MBRC-101 using 1 or more dosing regimens
• To identify potential RP2Ds and regimens of MBRC-101

Phase 1b

• To evaluate the safety of MBRC-101 at potential OBRDs, RP2Ds and dosing regimens
• To evaluate preliminary clinical activity of MBRC-101 at potential OBRDs and dosing regimens

Phase 2

• To evaluate the efficacy of MBRC-101 at the RP2D

Secondary Objectives:

Phase 1

• To evaluate other measures of preliminary clinical activity of MBRC-101

Phase 2

• To evaluate other measures of clinical activity
• To evaluate the safety of MBRC-101 at RP2Ds and dosing regimens

Phase 1/1b and Phase 2

• To characterize single and multiple-dose PK profiles of MBRC-101
• To evaluate incidence and persistence of anti-MBRC-101 Ab formation
• To evaluate biomarkers of clinical response and resistance, safety, pharmacodynamic activity, and/or mechanism of action of MBRC-101