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) PAUSED
  • Cohort 3: Bladder and urothelial tract WAITLIST CLOSED (0 SLOTS AVAILABLE)
  • Cohort 4: Cervical (combined with cohort 5) 3 SLOTS AVAILABLE
  • Cohort 5: Endometrial (combined with cohort 4) 3 SLOTS AVAILABLE
  • Cohort 6: Other solid tumor types (excl. 1-5 and NSCLC) CLOSED
  • Cohort 7: Breast STAGE 2 OPEN (6 SLOTS AVAILABLE)
• 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

1. ECOG performance status of 0/1. 

2. Homozygous MTAP or CDKN2A-deletion identified through molecular testing from a locally certified laboratory. If results for both mutations are available and discrepant, the result on MTAP deletion has priority or the result for CDKN2A deletion. (MTAP predicted no longer permitted as of 27/11/25)

3. Exhausted available standard of care treatments known to be beneficial for the tumour type or for whom these treatments are not acceptable and for whom this trial is a reasonable option. 

4. Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block (ideally no older than 6 months) must be available. An FFPE block is strongly preferred. Participants without archived tumor available may be allowed to enroll by undergoing tumor biopsy before BAY 3713372 dosing if deemed safe and feasible by the investigator.

5. At least 18 years of age

Exclusion Criteria

1. 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).

2. Presence of central nervous system (CNS) tumors including progressing, novel and/or symptomatic metastatic brain disease.

    Participants with treated brain metastases that are asymptomatic at screening are eligible if all of the following criteria are met:

• There is no evidence of progression (new or enlarging brain metastases) for at least 6 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.

• Participants must be off or receiving low-dose of corticosteroids (≤10 mg prednisone or equivalent) for 7 days prior to the first administration of study intervention

3. Patients with glioblastoma multiforme.

4. Patients with a history or presence of haematological malignancies unless curatively treated with no evidence of disease ≥ 2 years.

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: 

*Recruitment currently paused. Waitlist Open. 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 as monotherapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.

Eligible Population: 

NOTE: Dose escalation in progress and slot availability at each dose level is limited

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 PRMT5 inhibitor or methionine adenosyltransferase 2a (MAT2A) inhibitor

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 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. This will be conducted as four open-label subprotocols (F8394-201A; F8394-201B; F8394-201C; F8394-201D) under one master protocol.

Eligible Population: 

Inclusions:

All subprotocols:

• 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 A: 

• BRAF gene fusion in Solid Tumors and CNS Primary

Subprotocol B:

• BRAF V600E Mutated Recurrent Primary CNS Tumors including but not limited to the following:
  • 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);
• Had prior treatment with radiotherapy and/or first-line chemotherapy or concurrent chemoradiation therapy, or intolerant to available therapies; 

Subprotocol C:

• Rare BRAF V600E Mutated Solid Tumors (non-CNS) including ovarian and other gynecologic cancers, cholangiocarcinoma, small intestinal, and other gastrointestinal cancers (other than colorectal adenocarcinoma) and neuroendocrine cancers;

Subprotocol D:

• 18-65 years of age
• Cutaneous metastatic melanoma, thyroid cancer or NSCLC harboring a BRAF V600E mutation;
• Participants with cutaneous melanoma have previously received and not tolerated a BRAF inhibitor, while participants with thyroid cancer are MAPK inhibitor naïve;

Exclusions:

All subprotocols:

• Participants with co-occurring NF-1 alteration and/or RAS-related mutations;

Subprotocol A & B:

• Prior treatment with BRAF, ERK, and/or MEK inhibitor(s);

Subprotocol C:

• Diagnosis of colorectal adenocarcinoma or pancreatic ductal adenocarcinoma (neuroendocrine or acinar tumors are eligible);
• Diagnosis of BRAF V600E-mutated cutaneous melanoma, thyroid cancer (ATC and PTC), or NSCLC; 
• Participant has CNS metastases;
• Participants with known pathogenic driver molecular alterations (eg, NF-1 alteration and/or RAS, and MAPK pathway associated alterations), constitutive activation mutations in the hormone receptor genes (eg, ARV7 in prostate cancer and ESR1 in breast cancer) or clear acquired activating mutations from prior therapies;
• Prior treatment with BRAF, pan-RAF, ERK, and/or MEK inhibitor(s);
• Tyrosine kinase inhibitor(s) and/or targeted therapies are allowed (other than BRAF/MAPK pathway inhibitors);

Subprotocol D:

• Participants with known acquired driver mutations, including from prior MAPK pathway targeted therapies;
• Prior tyrosine kinase inhibitor(s) and/or targeted therapies are allowed;
• Participant has CNS metastases;

Substudy status: Recruiting

Registration number: NCT05503797

Title: Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination With Pembrolizumab Versus Investigator's Choice in HLA-A*02:01-positive Participants With Previously Treated Advanced Melanoma (TEBE-AM)

The purpose of this study is to evaluate the efficacy and safety of tebentafusp-based regimens, including tebentafusp monotherapy and in combination with anti-PD1 vs investigator choice (including clinical trials of investigational agents, salvage therapy per local standard of care [SoC], best supportive care [BSC] on protocol survivor follow up) in patients with advanced non-ocular melanoma.

Eligible Population: 

Inclusion criteria:

• HLA-A*02:01-positive
• Unresectable Stage III or Stage IV non-ocular melanoma
• ECOG 0 or 1

Exclusion criteria:

• diagnosis of ocular or metastatic uveal melanoma
• known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
• received prior treatment with a licensed or investigative Immune-mobilizing monoclonal T-cell receptor Against Cancer (ImmTAC) medication
• have not progressed on treatment with an anti-PD(L)1 mAb
• have not received prior treatment with an approved anti-CTLA-4 mAb
• a BRAF V600 mutation, who have not received a prior BRAF/MEK TKI regimen 
• history of allogenic tissue/solid organ transplant

Substudy status: Recruiting

Registration number: NCT05549297

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.

Exclusion criteria:

• Prior treatment with a methionine adenosyltransferase 2a inhibitor or a PRMT5 inhibitor.
• Known active central nervous system (CNS) or leptomeningeal metastases. Patients with previously treated brain or meningeal metastases may be eligible if they are asymptomatic, stable (without evidence of progression for at least 4 weeks by brain imaging prior to the first dose of study treatment), do not require local treatment (eg, surgery or radiation), or do not require excessive steroids (defined as a prednisolone dose ≤10 mg daily or equivalent) for at least 2 weeks prior to the first dose of study treatment. Note: This does not apply to participants with primary CNS tumors,who should otherwise have no neurologic symptoms or complications that in the opinion of the investigator hinders study participation.
• Bone and soft tissue primaries exclusionary.

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.

Key inclusion criteria:

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

Key exclusion criteria:

• Known KRAS mutation

Substudy status: Recruiting

Registration number: NCT04585750

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)

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

Substudy status: Recruiting

Registration number: NCT06127407

Title: An Open-label, Phase 1 Study to Assess Safety, Tolerability, Dosimetry, Pharmacokinetics and Imaging Properties of 89Zr-olaratumab (89Zr-TLX300-CDx) in Participants With Soft Tissue Sarcoma (ZOLAR).

Open-label, first-in-human Phase 1 imaging study will include three parts: proof-of concept tumour targeting of 89Zr-TLX300-CDx (Part A), assessment of 89Zr-TLX300-CDx biodistribution and tumour uptake (Part B) and radiation dosimetry (Part C).  The purpose of this study is to assess safety, tolerability, dosimetry, pharmacokinetics and imaging properties of 89Zr-olaratumab (89Zr-TLX300-CDx) in participants with STS (patients with indications other than STS, that could be PDGFRα, will also be assessed for inclusion on a case-by-case basis by the Sponsor). 

Eligible Population: 

INCLUSION 

• Histologically confirmed diagnosis of soft tissue sarcoma (STS)
• At least one mass of > 2cm in largest diameter seen on standard of care imaging
• Part A: Participants must have tumour PDGFRα expression confirmed by IHC (GIST patients will be exempt from this criterion). Participants must have consented to provide prior/archival FFPE tumour tissue
• Part B and C: All participants will be included regardless of their PDGFRα expression status on prior/archival tissue. Participants must have consented to provide prior/archival FFPE tumour tissue
• ECOG 0-2

EXCLUSION 

• IgE antibodies against galactose-α-1,3-galactose (α-Gal) above the ULN, >0.7 kU/L

Substudy status: Recruiting

Registration number: NCT06537596