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”)

Primary Objectives:

• To assess the safety and tolerability of BL-M07D1 in metastatic or unresectable HER2-expressing tumors
• To determine the MTD if reached or MAD and two or more RDEs of BL-M07D1

Secondary Objectives:

• To characterize the pharmacokinetics of BL-M07D1, total anti-HER2 antibody, and payload (Ed-04)
• To investigate the antitumor activity of BL-M07D1

Primary Objectives:

• To evaluate the antitumor activity of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors

Secondary Objectives:

• To assess other antitumor efficacy parameters of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors
• To evaluate the safety and tolerability of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors
• To evaluate the PK of zanidatamab
• To evaluate the immunogenicity of zanidatamab
• To evaluate participant-reported tolerability of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors

Primary Objectives:

• To evaluate the safety by rate of DLTs and AEs of [212Pb]VMT-α-NET in subjects with NETs.
• To determine the recommended phase 2 dose (RP2D) of [212Pb]VMT-α-NET in PRRT-naïve subjects with NETs.
• To determine the PK properties of [212Pb]VMT-α-NET.
• To determine the ORR by RECIST v1.1 in subjects with NETs receiving [212Pb]VMT-α-NET in the dose-expansion phase.

Secondary Objectives:

• To determine the ORR by RECIST v1.1 in subjects with NETs receiving [212Pb]VMT-α-NET in the dose-escalation phase.
• To determine the DOR by RECIST v1.1 in subjects with NETs receiving [212Pb]VMT-α-NET.
• To determine the PFS by RECIST v1.1 in subjects with NETs receiving [212Pb]VMTα-NET.
• To determine the OS in subjects with NETs receiving [212Pb]VMT-α-NET.

Primary Objectives:

• To compare OS between ivonescimab combined with platinum-doublet chemotherapy and pembrolizumab combined with platinum-doublet chemotherapy
• To compare investigator assessed progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 between ivonescimab combined with platinum-doublet chemotherapy and pembrolizumab combined with platinum- doublet chemotherapy

Secondary Objectives:

• To compare the objective response rate (ORR), disease control rate (DCR), and duration of response (DoR) between ivonescimab combined with platinum-doublet chemotherapy versus pembrolizumab combined with platinum-doublet chemotherapy, as assessed by investigator, based on RECIST v1.1
• To evaluate the safety and tolerability of ivonescimab in combination with platinumdoublet chemotherapy and compare to pembrolizumab combined with platinum-doublet chemotherapy
• To evaluate the pharmacokinetic profile of ivonescimab in combination with platinumdoublet chemotherapy
• To evaluate the immunogenicity of ivonescimab

Primary Objectives:

• To compare OS between ivonescimab versus pembrolizumab
• To compare PFS assessed by the Independent Radiology Review Committee (IRRC) based on RECIST v1.1 between ivonescimab and pembrolizumab

Secondary Objectives:

• To compare the ORR, DCR, and DoR between ivonescimab versus pembrolizumab, as assessed by the IRRC, based on RECIST v1.1
• To evaluate the safety and tolerability of ivonescimab and compare to pembrolizumab
• To evaluate the PK profile of ivonescimab
• To evaluate the immunogenicity of ivonescimab

Primary:

In the RAS (G12X-C) population, i.e., RAS G12X excluding G12C:

• To compare the treatment effect of RMC-6236 versus docetaxel on:
  • PFS (per Investigator)
  • OS

Key Secondary

In the RAS (MUT) population:

• To compare the treatment effect of RMC-6236 versus docetaxel on:
  • PFS (per Investigator)
  • OS

In the RAS (G12X-C) and RAS (MUT) populations:

• To compare the treatment effect of RMC-6236 versus docetaxel on objective response (per Investigator)

Other Secondary

In the RAS (G12X-C) and RAS (MUT) populations:

• To compare the treatment effect of RMC-6236 versus docetaxel on:
  • PFS (per BICR)
  • Objective response (per BICR)

In the RAS (G12X-C) and RAS (MUT) populations:

• To compare the treatment effect of RMC-6236 versus docetaxel on:
  • DOR (per Investigator and per BICR)
  • TTR (per Investigator and per BICR)

In the RAS (G12X-C) and RAS (MUT) populations:

• To compare the treatment effect of RMC-6236 versus docetaxel on QoLs using EORTC QLQ-LC13 and EORTC QLQ-C30

In the RAS (G12X-C) and RAS (MUT) population:

• To compare safety and tolerability of RMC-6236 versus docetaxel

In the RAS (MUT) population:

• To characterize the PK of RMC-6236