Clinical Trials Actively Recruiting

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 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 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 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

Safety Run-in Period

Primary Objectives:

• To assess the safety and tolerability of osimertinib in combination with Dato-DXd in all dosed safety run-in participants.

Secondary Objectives:

• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd by assessment of ORR in all dosed safety run-in participants with measurable disease at baseline.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd by assessment of DoR in all dosed safety run-in participants with measurable disease at baseline.
• To assess the PK of osimertinib and DatoDXd.
• To investigate the immunogenicity for DatoDXd

Randomisation Period

Primary Objectives:

• To demonstrate the superiority of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of PFS by BICR in all randomised participants.

Secondary Objectives:

• To demonstrate the superiority of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of OS in all randomised participants.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of CNS PFS by CNS BICR in participants with CNS metastases at baseline.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of PFS by investigator in all randomised participants.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of ORR in all randomised participants with measurable disease at baseline.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of DoR in all randomised participants with measurable disease at baseline.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd relative to osimertinib on the prevention of CNS metastases.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd relative to osimertinib by assessment of PFS2 in all randomised participants
• To assess the PK of osimertinib and DatoDXd.
• To investigate the immunogenicity of DatoDXd.
• To compare the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples.
• To demonstrate the effectiveness of osimertinib in combination with Dato-DXd vs. osimertinib monotherapy based on the cobas® EGFR Mutation Test v2 plasma screening test result for Ex19del or L858R EGFR mutations.

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:

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

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.