Clinical Trials Actively Recruiting

Primary Objective(s):

• To compare progression-free survival in participants with metastatic papillary renal cell carcinoma (mPRCC) randomized to cabozantinib with atezolizumab versus cabozantinib alone.
   

Secondary Objective(s):

• To compare overall survival in participants with mPRCC randomized to cabozantinib with atezolizumab versus cabozantinib alone.
• To compare RECIST objective response rate (confirmed and unconfirmed, complete and partial response) in participants with mPRCC randomized to cabozantinib with atezolizumab versus cabozantinib alone.
• To evaluate the quantitative & qualitive adverse events observed in each treatment arm.

Primary Objectives:

• To determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical BCG vs GEMDOCE.
   

Secondary Objectives:

• To compare changes in cancer-specific and bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE.
• To determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.
• To determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.
• To determine the safety and toxicity of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.

Primary Objectives:

De-Intensification Study:

• To determine whether men with NCCN high risk prostate cancer who are in the lower 2/3 of Decipher genomic risk (< 0.85) can be treated with 12 months ADT plus RT instead of 24 months ADT+RT and experience non-inferior metastasis-free survival.

Intensification Study:

• To determine whether men with NCCN high risk prostate cancer who are in the upper 1/3 of Decipher genomic risk (>0.85) or have node-positive disease by conventional imaging (MRI or CT scan) will have a superior metastasis-free survival (MFS) through treatment intensification with apalutamide added to the standard of RT plus 24 month ADT.

Secondary Objectives for both De-Intensification and Intensification Studies:

• To compare overall survival (OS) between the standard of care (RT plus 24 months of ADT) and either the de-intensification (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare time to PSA failure or start of salvage treatment between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 24 months of ADT) and either the deintensification arm  RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare MFS judged based on either standard or molecular imaging between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plusapalutamide).
• To compare prostate cancer-specific mortality between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare testosterone levels at the time of PSA failure and metastases between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare time to testosterone recovery (defined as a T>200) between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare adverse events, both clinician-reported using CTCAE v5.0 and patientreported using PRO-CTCAE items, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).

Primary Objective:

De-Intensification Study:

• To determine whether men with National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk (UIR) prostate cancer and lower Decipher genomic risk (Decipher score < 0.40) treated with RT alone instead of 6 months ADT + RT experience non-inferior rate of distant metastasis.

Intensification Study:

• To determine whether men with NCCN UIR prostate cancer who are in the higher genomic risk (Decipher score ≥0.40) will have a superior metastasis-free survival through treatment intensification with darolutamide added to the standard of RT plus 6 months ADT.

Secondary Objectives:

• To compare overall survival (OS) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare time to PSA failure between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare metastasis free survival (MFS) based on conventional imaging between the standard of care (RT plus 6 months of ADT) and de-intensification intervention (RT alone).
• To compare MFS based on either conventional and/or molecular imaging between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare cumulative incidence of locoregional failure based upon conventional imaging and/ or biopsy between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months ADT plus darolutamide) interventions.
• To compare cumulative incidence of distant metastasis based upon conventional imaging between standard of care (RT plus 6 months of ADT) and intensification intervention (RT plus 6 months ADT plus darolutamide).
• To compare cumulative incidence of distant metastasis based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare prostate cancer-specific mortality between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare sexual and hormonal related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare fatigue, as measured by the PROMIS-Fatigue instrument, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

Phase 1 (Dose Escalation)

Primary Objectives:

• To evaluate the safety and tolerability of DB-1311.
• To determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of DB-1311.

Secondary Objectives:

• To assess the preliminary antitumor activity of DB-1311.
• To characterize the Pharmacokinetics (PK) of DB-1311 (DB-1311 antibodydrug conjugate [ADC], total anti- B7-H3 antibody, unconjugated payload P1021).
• To assess the immunogenicity of DB1311 in targeted subjects.

Phase 2a (Dose Expansion)

Primary Objectives:

• To assess the safety and tolerability of DB-1311 as monotherapy in targeted subject populations.
• To assess the effectiveness of DB-1311 as monotherapy by assessment of objective response rate (ORR) by investigator.

Secondary Objectives:

• To further assess the PK of DB-1311 (DB-1311 ADC, total anti-B7-H3 antibody, unconjugated payload P1021).
• To evaluate the prevalence and incidence of anti-drug antibody (ADA) against DB1311 in serum via a validated assay.
• To evaluate the preliminary efficacy of DB-1311 with additional efficacy parameters.

Phase 1a Dose Escalation

Primary Objectives:

• To assess the safety and tolerability of BGB-43395 alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.
• To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended dose(s) for expansion (RDFE[s]) of BGB-43395 alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.

Secondary Objectives:

• To assess the preliminary anticancer activity of BGB-43395 alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.
• To characterize the PK of BGB-43395 and its metabolite, BGB-48579, alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.

Phase 1b: Dose Expansion Objectives and Endpoints

Primary Objectives:

• To assess the antitumor activity in patients treated with BGB-43395 alone or as part of combination therapies in selected tumor cohorts.

Secondary Objectives:

• To further assess the antitumor activity in patients treated with BGB-43395 alone or as part of combination therapies in selected tumor cohorts.
• To further characterize the safety and tolerability of BGB-43395 alone or as part of combination therapies.
• To further characterize the pharmacokinetics (PK) of BGB-43395 and its metabolite, BGB-48579, with combination therapies.

Primary Objectives:

• To identify the maximum tolerated dose (MTD) and/ or recommended Phase 2 dose (RP2D), and evaluate the safety, tolerability and dose-limiting toxicities (DLTs) of HC-7366 in combination with belzutifan in patients with locally advanced or metastatic RCC with predominantly clear cell histology (ccRCC), irrespective of VHL gene mutation status (combination only).

Secondary Objectives:

• To assess the potential antitumor activity of HC-7366 in combination with belzutifan by response, disease stabilization, and survival outcomes by assessing:
  • 1. Overall response rate (ORR) per RECIST v1.1
  • 2. Duration of response (DOR)
  • 3. Disease control rate (DCR: CR or PR or stable disease)
  • 4. Time to Response (TTR)
  • 5. Median progression free survival (PFS) and PFS at six months
  • 6. Median overall survival (OS) and 1-yr OS
• To determine the plasma concentration and PK parameters following single and multiple doses of HC-7366 alone or in combination with belzutifan administered to patients with locally advanced or metastatic RCC with predominantly clear cell histology, irrespective of VHL gene mutation status (PK parameters of both HC-7366 and belzutifan will be measured)
• To characterize HC-7366 monotherapy and in combination with belzutifan in patients with ccRCC

Primary Objectives:

• To compare DFS between Group A and Group B

Secondary Objectives:

• To compare TTNT (local or systemic) between study treatments
• To compare HG RFS between study treatments
• To compare PFS between study treatments
• To compare the rate of diagnostic and therapeutic invasive urological interventions after study treatment
• To assess safety and tolerability
• To compare OS between study treatments
• To compare participant-reported disease- and treatment-related symptoms and impacts on functioning between study treatments

Part I: Dose Escalation Phase

Primary Objectives:

• To evaluate the safety and tolerability of BGC515 Capsules in patients with malignant mesothelioma (MM), epithelioid hemangioendothelioma (EHE), or other advanced solid tumors.
• To explore the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD).

Secondary Objectives:

• To evaluate the pharmacokinetics (PK) of BGC515 Capsules in patients with MM, EHE, or other advanced solid tumors.
• To preliminarily evaluate the efficacy of BGC515 Capsules in patients with MM, EHE, or other advanced solid tumors.

Part II: Dose Expansion Phase

Primary Objectives:

• To further evaluate the safety and tolerability of BGC515 Capsules in patients with MM, EHE, glioblastoma, or other advanced solid tumors including those with NF1/2 deficiency, YAP/TAZ fusion, LATS1/2 mutation, MST1/2 mutation, so as to determine the recommended phase 2 dose (RP2D).
• To evaluate the preliminary efficacy of BGC515 Capsules in patients with MM, EHE, glioblastoma, or other advanced solid tumors including those with NF1/2 deficiency, YAP/TAZ fusion, LATS1/2 mutation, MST1/2 mutation.

Secondary Objectives:

• To evaluate the PK of BGC515 Capsules in patients with MM, EHE, glioblastoma, or other advanced solid tumors including those with NF1/2 deficiency, YAP/TAZ fusion, LATS1/2 mutation, MST1/2 mutation.

Phase 1a dose escalation

Primary Objectives:

• To determine the MTD/MAD and evaluate the safety and tolerability of GSK5764227 in participants with advanced solid tumors.

Secondary Objectives:

• To evaluate the PK profile of GSK5764227 in participants with advanced solid tumors.
• To evaluate the clinical activity of GSK5764227 in participants with advanced solid tumors
• To evaluate the immunogenicity of GSK5764227 in participants with advanced solid tumors.To evaluate the immunogenicity of GSK5764227 in participants with advanced solid tumors.

Phase 1b dose expansion

Primary Objectives:

• To evaluate the clinical activity of GSK5764227 in participants with ES-SCLC or advanced solid tumors.

Secondary Objectives:

• To evaluate the safety and tolerability of GSK5764227 in participants with ES-SCLC or advanced solid tumors
• To evaluate additional measures of clinical benefit of GSK5764227 in participants with ES-SCLC or advanced solid tumors.
• To evaluate the PK profile of GSK5764227 in participants with ES-SCLC or advanced solid tumors.
• To evaluate the immunogenicity of GSK5764227 in participants with ES-SCLC or advanced solid tumors.