Title: A Study to Learn More About How Well Treatment With BAY2927088 Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2) (panSOHO)

A Phase 2 Open-label Basket Study to Evaluate the Efficacy and Safety of Orally Administered Reversible Tyrosine Kinase Inhibitor BAY 2927088 in Participants With Metastatic or Unresectable Solid Tumors With HER2-activating Mutations

Eligible Population: 

Inclusion Criteria

• Documented histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumor cancer:
  • Cohort 1: Colorectal CLOSED
  • Cohort 2: Biliary tract (incl. gallbladder and intra/extrahepatic cholangiocarcinoma) CLOSED
  • Cohort 3: Bladder and urothelial tract CLOSED
  • Cohort 4: Cervical (combined with cohort 5) 7 slots available
  • Cohort 5: Endometrial (combined with cohort 4) 7 slots available
  • Cohort 6: Other solid tumor types (excl. 1-5 and NSCLC) CLOSED
  • Cohort 7: Breast CLOSED
• Documented activating HER2 mutation.
• Patients who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments.

Exclusion Criteria

• Primary diagnosis of non-small cell lung cancer (NSCLC).
• Prior treatment with a HER2 tyrosine kinase inhibitor (TKI).
• Active brain metastases.
• Known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for five years since initiation of that therapy. Exception: the following cancer types are acceptable within five years if curatively treated or under surveillance:
  a. in situ cancers (eg cervix, breast, colon or skin),
  b. superficial bladder cancer (Ta, Tis and T1),
  c. limited-stage prostate cancer,
  d. basal or squamous cancers of the skin

Substudy status: Recruiting

Registration number: NCT06760819

Title: A first-in-human study to evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics and preliminary clinical activity of BAY 3713372, a novel 2nd generation PRMT5 inhibitor, in participants with MTAP-deleted solid tumors.

In cancer cells harboring MTAP deletion, MTA accumulates leading to partial inhibition of PRMT5. BAY 3713372 is an MTA-cooperative PRMT5 inhibitor that is selectively efficacious against MTAP deleted cancer cells sparing cells that have low levels of intracellular MTA. This human study will assess safety, PK, PD and preliminary anti-tumor activity of BAY 3713372 in participants with MTAP-deleted solid tumors. 

Eligible Population: 

Inclusion Criteria

• Non-small cell lung cancer (NSCLC) in the second-line or later setting or
• Pancreatic ductal adenocarcinoma (PDAC) in the second-line or later setting
• Homozygous MTAP-deletion identified through molecular testing from a locally certified laboratory. 
• Participants with treated brain metastases are eligible if all of the following conditions are met: 
  • Asymptomatic.
  • No evidence of interim progression (new or enlarging brain metastases) for at least 4 weeks between completion of CNS-directed therapy and initiation of study treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period, are eligible if all of the following criteria are met:
   • Metastases are limited to the cerebellum or supratentorial region (i.e. no metastases to the midbrain, pons, medulla or spinal cord).

Exclusion Criteria

• Previous additional cancer else than the one evaluated in this study within the past 2 years, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, localized prostate cancer or other tumors (including localised in situ carcinoma considered as completely resected and cured).
• Patients with a history or presence of haematological malignancies unless curatively treated with no evidence of disease ≥ 2 years.
• Prior treatment with a MAT2A or a PRMT5 inhibitor. 

Substudy status: Recruiting

Registration number: NCT06914128

Title: Phase 1 Study of a SOS1 Inhibitor, BAY3498264, in Combination in Participants With Advanced KRAS G12C-mutated Solid Tumors

A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRAS G12C Mutation

Eligible Population: 

*Now prioritising CRC patients naïve to KRAS G12C inhibitors and any number of prior lines of therapy (at least 1)*

*PLEASE CONTACT PI FOR INQUIRIES*

Inclusion Criteria:

• Histologically confirmed solid tumor malignancy with documented KRAS G12C mutation.
• ECOG of 0 to 2 and life expectancy of at least 12 weeks.
• Documented disease progression after treatment with at least 1 prior standard of care (SoC) systemic therapy other than a G12C inhibitor for locally advanced or metastatic disease.
• Prior G12C inhibitor treatment is permitted. Participants receiving prior G12C inhibitor therapy must have documented disease progression after treatment, or have discontinued that treatment due to intolerance.

Exclusion Criteria:

• Active central nervous system (CNS) tumors including metastatic brain disease at the time of screening.
• Additional malignancy within the past 3 years, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, localized prostate cancer and other tumors that in the opinion of the investigator, in agreement with the sponcer are considered cured or not immediately life-threatening, and will not interfere with the scientific goals of the study.

Substudy status: Recruiting

Registration number: NCT06659341

Title: Vitrakvi (Larotrectinib) Patient Access Program

Vitrakvi (larotrectinib) has provisional approval in Australia for the treatment of adult patients with locally advanced or metastatic solid tumours.

Eligible Population: 

• The condition must be positive for a NTRK gene fusion confirmed by NGS or FISH.
• For patients aged under 18 years, must be diagnosed with a solid tumour or for patients aged 18 year or over, must be diagnosed with solid tumour that harbours NTRK gene fusions at high frequency of >75%.
• Disease must be metastatic or unresectable locally advanced.
• For adults with low frequency NTKR fusion tumour, patients must have progressed on or after one or more systemic therapies appropriate for their tumour type, in the locally advanced or metastatic setting or would be unlikely to tolerate SoC therapy.
• Patient must not have received prior treatment with TRK inhibitor
• ECOG 3 or less.

For more information, please contact Bayer medical affairs via email: medaffairs.anz@bayer.com

Substudy status: Recruiting

Registration number: LarotrectinibAP

Title: A Phase 1a/b Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BGB-58067, an MTA-Cooperative PRMT5 Inhibitor in Patients With Advanced Solid Tumors

This is an open-label, multicenter, first-in-human dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 alone, in combination with BG-89894 (discontinued), and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.

Eligible Population: 

Inclusion Criteria

• Participants with advanced, metastatic, or unresectable non-CNS solid tumors and grade II-IV gliomas, who have previously received standard systemic therapy or for whom treatment is not available or not tolerated.
• Evidence of homozygous loss of MTAP or lost MTAP expression in the tumor tissue.
• ECOG 0 or 1.

Exclusion Criteria

• Prior treatment with any methylthioadenosine (MTA)-cooperative PRMT5 inhibitor or methionine adenosyltransferase 2a (MAT2A) inhibitor.
• Active leptomeningeal disease or symptomatic spinal cord compression.

Substudy status: Recruiting

Registration number: NCT06589596

Title: A Phase 2 Study to Assess the Efficacy and Safety of FORE8394, an Inhibitor of BRAF Class 1 and Class 2 Alterations, in Participants With Cancer Harboring BRAF Alterations

The objective of this study is to evaluate the efficacy and safety of plixorafenib in participants with locally advanced or metastatic solid tumors, or recurrent or progressive primary central nervous system (CNS) tumors harboring BRAF fusions, or in participants with rare solid tumors, melanoma, thyroid, or recurrent primary CNS tumors harboring BRAF V600E mutation. 

Eligible Population: 

Inclusion criteria

Subprotocol A: CLOSED

• Histologic diagnosis of a solid tumor or primary CNS tumor.
• Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing.
• ECOG 0, 1, or 2
• Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.

Subprotocol B: CLOSED

• Histological diagnosis of a primary CNS tumor, including but not limited to the following:
  • Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor (including glioblastoma, anaplastic astrocytoma, high grade astrocytoma with piloid features, pilocytic astrocytoma, gliosarcoma, anaplastic pleomorphic xanthoastrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, not otherwise specified [NOS], ganglioglioma, or recurrent LGG).
• Documented BRAF V600E mutation in tumor and/or liquid biopsy.
• Participants must have unresectable, locally advanced or metastatic disease that had prior treatment with radiotherapy and/or first-line chemotherapy or concurrent chemoradiation therapy or intolerant to available therapies. 
• ECOG 0, 1, or 2
• Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.

Subprotocol C:

• Histologic diagnosis of a rare BRAF V600E-mutated solid tumor that is unresectable, locally advanced or metastatic.
• ECOG 0, 1, or 2
• Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test.
• Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.

Subprotocol D: CLOSED

• Male and female, ≥18 years of age.
• ECOG 0, 1 and life expectancy >3 months.
• Histologic diagnosis of a solid tumor harboring a BRAF V600E mutation and not eligible for other subprotocols.
• Evidence of BRAF V600E mutation in tumor and/or blood detected by genomic tests.
• Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.

Exclusion criteria

Subprotocol A:

• Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease.
• Prior treatment with a MEK inhibitor.
• Tyrosine kinase inhibitor(s) and/or targeted therapies are allowed (other than BRAF/MAPK pathway inhibitors per Exclusion Criteria 3 and 4) and will be restricted to no more than the number of lines of therapy that are consistent with standard treatment guidelines.
• Malignancy with co-occurring activating RAS mutation(s) at any time.

Subprotocol B:

• Prior treatment with BRAF, ERK, and/or MEK inhibitor(s).
• Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations.

Subprotocol C:

• Diagnosis of colorectal adenocarcinoma or pancreatic ductal adenocarcinoma (neuroendocrine or acinar tumors are eligible).
• Diagnosis of BRAF V600E-mutated cutaneous melanoma, papillary thyroid cancer, or NSCLC.
• Participant has CNS metastases.
• Prior treatment with BRAF, ERK, and/or MEK inhibitor(s), unless otherwise specified for specific tumor types (i.e. low grade serous or borderline ovarian cancer).
• Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations.
• Participants with prostate, breast, or gynecologic cancers with known activating mutations that lead to constitutive hormone receptor activation (AR-V7, ESR1).

Subprotocol D:

• Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations or other co-occurring driver mutations.
• Participant has a non-CNS solid tumor with CNS metastases.

Substudy status: Recruiting

Registration number: NCT05503797

Title: A Phase 1a/1b Study Evaluating the Clinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Efficacy of PEP08 as Monotherapy and Combination Therapy in MTAP-Del Advanced or Metastatic Solid Tumors.

This is a first-in-human dose escalation and dose expansion Phase 1a/1b, multicenter, open-label, multiple-dose clinical study designed to evaluate the clinical safety, tolerability, PK, PD, and preliminary anti-tumor efficacy of PEP08 as monotherapy and combination therapy, and to establish the MTD, if any, and/or RP2D, in patients with MTAP-del advanced or metastatic solid tumors.

Eligible Population: 

Inclusion criteria

• Evidence of homozygous deletion of the MTAP gene detected in tumor tissue, including:
  • Documented homozygous MTAP deletion confirmed by next generation sequencing (NGS) technique or fluorescence in situ hybridization (FISH); or
  • Documented homozygous CDNK2A or CDKN2B deletion identified by NGS or FISH technique accompanied by confirmed MTAP loss by immunohistochemistry.
• Participants must have previously received standard treatment for their cancer type, and either experienced disease progression, be refractory, or be intolerant to such therapies.
• At least one measurable lesion is required, evaluated by standard imaging criteria (RECIST v1.1).

Exclusion criteria

• Prior treatment with a methionine adenosyltransferase 2a inhibitor or a PRMT5 inhibitor.
• Active or unstable brain or meningeal metastases, unless previously treated and stable without needing local treatment or high-dose steroids.
• Active HIV, hepatitis B or C infections that are not well-controlled.

Note. The study is no longer accepting bone and soft tissue primaries.

Substudy status: Recruiting

Registration number: NCT06973863

Title: The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

This Phase 1/2 study will assess the safety, tolerability, and efficacy of multiple dose levels of PC14586 (INN: rezatapopt) alone (monotherapy) and in combination with pembrolizumab in participants with advanced solid tumors containing a TP53 Y220C mutation.

Eligible Population: 

Phase 2 (PC14586 monotherapy) open to recruitment in Australia.

Inclusion Criteria:

• Advanced solid malignancy with a TP53 Y220C mutation (excl. primary CNS). Slots are now limited to the following tumour types:
  • Ovarian (~3 remaining)
  • Endometrial (~4 remaining)
  • Lung (CLOSED)
  • Breast (CLOSED)
  • Other solid tumors (CLOSED)
• ECOG 0 or 1.
• Previously treated with one or more lines of anticancer therapy and progressive disease.

Exclusion Criteria:

• Known KRAS mutation (ovarian cancer patients with a KRAS SNV are eligible for Phase 2).
• Primary CNS tumor.
• History of leptomeningeal disease or spinal cord compression.
• Brain metastases, unless neurologically stable and do not require steroids to treat associated neurological symptoms.

Substudy status: Recruiting

Registration number: NCT04585750

Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Breast Cancer

The aim of this study is to (cohort 2) focus on inoperable, locally advanced or metastatic, ER-positive, HER2-positive breast cancer with previous progression to standard-of-care anti-HER2 therapies, of which one was a trastuzumab-and-taxane-based systemic therapy (including in the early setting if recurrence occurred within 6 months of finishing adjuvant therapy) and one was a HER2-targeting antibody-drug conjugate or a HER2-targeting tyrosine kinase inhibitor. Cohort 3 will focus on inoperable, locally advanced or metastatic, ER+, HER2-negative, PIK3CA-mutated breast cancer with resistance to adjuvant endocrine therapy.

Eligible Population: 

Cohort 2 recruiting. Key inclusion criteria:

• Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection
• ER-positive, HER2-positive breast cancer
• Prior endocrine therapy in the advanced setting allowed, including fulvestrant if given more than 28 days prior to randomization, but excluding other selective estrogen receptor degraders (SERDs)

Cohort 3 recruiting. Key inclusion criteria:

• ER-positive, HER2-negative, PIK3CA-mutated breast cancer (confirmed from blood or tumor tissue)
• Patients for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study

Exclusion criteria for both cohorts: 

• History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
• Prior treatment with any of the protocol-specified study treatments
• Prior treatment with any SERD (Cohort 3) 

Substudy status: Recruiting

Registration number: NCT04802759

Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo As Maintenance Therapy After First Line Induction Therapy in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer

The aim of this study is to evaluate the efficacy and safety of inavolisib in combination with Phesgo (pertuzumab, trastuzumab, and rHuPH20 injection for subcutaneous use) compared with placebo in combination with Phesgo, as maintenance therapy, after induction therapy in participants with previously untreated HER2-positive advanced breast cancer (ABC).

Eligible Population: 

Participants with previously untreated HER2-positive, PIK3CA mutated locally advanced or metastatic breast cancer.

Substudy status: Recruiting

Registration number: NCT05894239

Title: A Phase I/Ib Global, Multicenter, Open-label Umbrella Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer

The aim of this study is to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or combinations, in participants with metastatic colorectal cancer (mCRC) whose tumors are biomarker positive as per treatment arm-specific definition. Eligible participants with mCRC will be enrolled into specific treatment arms based on their biomarker assay results.

Eligible Population: 

• Cohort H (OPEN): GDC-6036 + bevacizumab + FOLFOX (KRAS G12C altered tumors).
• Cohort I (OPEN): GDC-6036 + bevacizumab + FOLFIRI (KRAS G12C altered tumors).

Substudy status: Recruiting

Registration number: NCT04929223

Title: A Study Evaluating the Safety, Activity, and Pharmacokinetics of GDC-6036 in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

The aim of this study is to evaluate the safety, pharmacokinetics (PK), and activity of GDC-6036 combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).

Eligible Population: 

Patients with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation.

COHORT A2 OPEN: PD-L1 negative patients only; 1L treatment with Divarasib+Pembrolizumab

Substudy status: Recruiting

Registration number: NCT05789082

Title: A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Patients With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).

Eligible Population: 

Inclusion Criteria:

• No prior systemic treatment for advanced or metastatic NSCLC
• Documentation of the presence of a KRAS G12C mutation
• Documentation of known PD-L1 expression status in tumor tissue
• Availability of a representative tumor specimen

Exclusion Criteria:

• Radiation therapy including palliative RT to bone metastases within 2 weeks prior to randomization and RT to the lung >30Gy within 6 months prior to randomization
• Treatment with systemic immunosuppressive or immunostimulatory medications, including CD137 agonists and immune checkpoint inhibitors
• Prior treatment with KRAS G12C inhibitors or pan-KRAS/RAS inhibitors
• Known concomitant second oncogenic driver with available targeted treatment
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases

Substudy status: Recruiting

Registration number: NCT06793215

Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Treatment Combinations In Patients With Metastatic Breast Cancer

The aim of this study is to evaluate the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer.

Eligible Population: 

• Cohort 1  will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort). Recruitment Closed.

• Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line [2L] CIT-naive cohort). Recruitment Closed.

• Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative disease with PIK3CA mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (HR+cohort).

Referral to waitlist accepted:

Arm1: Inavo/Ribo400mg/Letro

Arm2: Inavo/Abema/Letro

• Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort). Recruitment Closed.

Substudy status: Recruiting

Registration number: NCT03424005

Title: A Phase 3, multicenter, double-blind, randomized, placebo-controlled study of ivosidenib in participants ≥18 years of age with locally advanced or metastatic conventional chondrosarcoma with an IDH1 mutation, untreated or previously treated with 1 systemic treatment regimen.

Study CL3-95031-007 (CHONQUER) is a Phase 3, international, multicenter, double-blind, randomized, placebo-controlled study of orally administered ivosidenib. Participants are required to have a histopathological diagnosis consistent with isocitrate dehydrogenase-1 (IDH1) gene-mutated, locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection.

Eligible Population: 

Inclusion Criteria:

• Have a histopathological diagnosis (fresh or banked tumor biopsy sample collected within the last 3 years). consistent with locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection.
• Have received 0 to 2 prior systemic treatment regimen in the advanced/metastatic setting for chondrosarcoma.
• Have had disease progression according to RECIST v1.1.
• Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available that was sourced from either a primary or metastatic tumor lesion) based on central laboratory testing (R132C/L/G/H/S mutation variants tested).

Exclusion Criteria:

• Are unable to swallow oral medication.
• Pregnant or lactating women.
• Are participating in another interventional study at the same time; participation in noninterventional registries or epidemiological studies is allowed.
• Have received prior therapy with an IDH1 inhibitor.
• Have received systemic anticancer therapy <2 weeks prior to randomization (for investigational or immune-based anticancer therapy <4 weeks).
• Have received radiotherapy <2 weeks prior to randomization.
• Have known symptomatic brain metastases requiring steroids >10 mg per day prednisone (or equivalent). Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued or reduced corticosteroid treatment <=10 mg per day for these metastases for at least 4 weeks and have radiographically stable disease of brain lesions for at least 3 months prior to randomization.

For further information visit: https://chonquer.com/en-au/hcp-vs-patient/ 

Substudy status: Recruiting

Registration number: NCT06127407

Title: A Multinational, Multicenter, Prospective, Randomized, Controlled, Open-Label, Phase 3 Study of Lutetium (177Lu) Rosopatamab Tetraxetan in Combination With Standard of Care Versus Standard of Care Alone in Patients With PSMA Positive Metastatic Castration-Resistant Prostate Cancer Previously After Androgen Receptor Pathway Inhibitor Treatment

The purpose of this study is to evaluate the efficacy and safety of 177Lu-TLX591 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with Androgen Receptor Pathway Inhibitor Treatment.

Eligible Population: 

Inclusion criteria:

• Male ≥18 years old with documented adenocarcinoma of the prostate.
• ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of ≥ 6 months.
• Have PSMA-positive (≥1 lesion with PSMA TLR≥2) metastatic disease that is progressing at study entry.
• Must have received a minimum of 12 weeks of prior therapy on an ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide), received in either the mCSPC, nmCRPC, or mCRPC treatment settings, with documented evidence of disease progression while receiving this ARPI. Progression must have occurred on the most recent ARPI. A prior ARPI may have been utilized, but no progression on the prior ARPI is allowed (e.g., ARPI was switched due to poor tolerability or due to adverse events). No washout period is required prior to enrollment into this trial. 

Exclusion criteria:

• Has PC associated with pathological findings consistent with small cell or any histology other than adenocarcinoma of the prostate. If there are minor (<20%) elements of neuroendocrine histology, this is acceptable;
• Has known brain metastases with long-axis ≥1cm, or liver metastases with long-axis ≥1cm, or lytic bone metastases with long-axis ≥1cm;
• Has received prior treatment with monoclonal antibody (mAb) J591 or HuJ591 or any other PSMA targeted therapy.
• Have received chemotherapy in the mCRPC or non-metastatic prostate cancer (nmCRPC) settings (note: prior docetaxel use in the mCSPC setting with CHAATERED or STAMPEDE regimens is permitted if the last dose of therapy was ≥6 months prior to screening and ≥4 cycles of docetaxel were administered).
• Has received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum-based anti-neoplastic drugs.

Substudy status: Recruiting

Registration number: NCT06520345