Title: A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors

The aim of Parts 1 and 2 of this study is to evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AMG 193 alone and in combination with docetaxel in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. The aim of Part 3 of this study is to evaluate the objective response rate (ORR) of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid tumors.

Eligible Population: 

The trial is open to enrolment for the following parts: 

• MTAP-null NSCLC (Part 1c)
• MTAP-null Esophageal /Gastric (Part 1l)
• MTAP-null Glioma (Part m)
• MTAP-null BTC (Part 1e) 4 slots remaining globally

Substudy status: Recruiting

Registration number: NCT05094336

Title: A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors

The main aims of this study are to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or the recommended combination dose of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors, and to evaluate the preliminary anti-tumor activity of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer (NSCLC).  

Eligible Population: 

• Evidence of homozygous loss of MTAP (null) and/or MTAP deletion by local next-generation sequencing (NGS) testing in a College of American Pathologist (CAP) or Clinical Laboratory Improvement amendments (CLIA) laboratory, or local equivalent, with central testing confirmation; or Central testing using IHC.
• Presence of advanced/metastatic solid tumor not amenable to curative treatment.
• Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists; or standard therapy has failed or not available/tolerated
• Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy, must include PD1 or programmed death-ligand 1 (PD-L1) inhibitors and platinum-based chemotherapy, and/or targeted therapy and chemotherapy (with or without PD1/PD-L1 inhibitors) if actionable oncogenic driver mutations were identified (i.e. EGFR, ALK, MET, RET, ROS1, KRASG12C). 

Substudy status: Recruiting

Registration number: NCT05975073

Title: An open-label, single-arm, multi-centre phase I/IIA clinician study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of SHR-A1904 in subjects with advanced solid tumors

The aim of this study is to assess the safety and tolerability of SHR-A1904 in subjects with advanced solid tumors, and to determine maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D), to assess preliminary efficacy of SHR-A1904, pharmacokinetic (PK) profile and immunogenicity of SHR-A1904 in subjects with advanced solid tumors.

Eligible Population: 

• Advanced relapsed or refractory solid tumors, either gastric and gastroesophageal junction (GEJ) cancer, who are intolerable to SoC, have progressed through all available treatment options, or for whom there is no efficacious treatment available. Subjects must have pathological classification (e.g., adenocarcinoma etc.) documented.
• Positive expression of Claudin 18.2 (>=50% of cells with 2+ or 3+ expression, either from fresh or archival tissue) is required prior to enrollment and participation in this study. Positivity for Claudin 18.2 is defined as tumor cells showing partial or complete membrane staining. The percentage of tumor cells at four different staining intensities will be estimated: 0 (no staining), 1+ (weak), 2+ (moderate), and 3+ (strong). The sum of all 4 percentages should equal 100%. The H-score is determined according to the H-Score formula: [1 x Percentage of tumor cells stained at 1+] + [2 x Percentage of tumor cells stained at 2+] + [3 x Percentage of tumor cells stained at 3+] = H-Score (range 0 or 1-300). Actual figure of Claudin 18.2 expression tested by IHC should be documented. 
• Patients who have received treatments with strong CYP3A4, CYP2D6, P-gp, or BCRP inhibitors or inducers within < 5 half-lives of the drug before the first dose of the study are not eligible.

Substudy status: Recruiting

Registration number: NCT05277168

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 III, Open-label, Randomized, Active-controlled, Multi-centre Trial Evaluating Orally Administered BI 1810631 Compared With Standard of Care as First-line Treatment in Patients With Unresectable, Locally Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer Harbouring HER2 Tyrosine Kinase Domain Mutations

The purpose of this study is to find out whether a medicine called BI 1810631 (zongertinib) can slow down the worsening of advanced non-small cell lung cancer better than the standard treatment available. Zongertinib may slow cancer cell growth by inhibiting HER2. This would prolong cancer re-occurrence and increase survival. Current standard treatment is pembrolizumab plus platinum-pemetrexed chemotherapy.

Eligible Population: 

• Advanced and/or metastatic non-squamous Non-small cell lung cancer (NSCLC)
• HER2 mutation in the Tyrosine kinase domain (TKD) 
• No prior systemic treatment for locally advanced or metastatic disease
• Exclusion of previous or concomitant malignancies other than the one treated in this trial within the last 5 years, except: effectively treated non-melanoma skin cancers; effectively treated carcinoma in situ of the cervix; effectively treated ductal carcinoma in situ; other effectively treated malignancy that is considered cured by local treatment

Substudy status: Recruiting

Registration number: NCT06151574

Title: A Phase II, multicentre, multicohort, open-label trial to evaluate the efficacy and safety of oral zongertinib (BI 1810631) for the treatment of selected HER2-mutated or overexpressed/amplified solid tumours

The purpose of this study is to find out whether a medicine called zongertinib helps people with advanced cancers with HER2 alterations. HER2 alterations can cause cancer. Zongertinib inhibits HER2.

Eligible Population: 

Patients with overexpressed/amplified HER2 tumours (with or without HER2 mutations) will be enrolled into one of six cohorts:

• Urothelial cancer (Cohort 1)
• Biliary tract cancer (Cohort 2)
• Uterine cancer (Cohort 3)
• Cervical cancer (Cohort 4)
• Non-squamous non–small cell lung cancer (NSCLC) (Cohort 5)
• Any other HER2 overexpressed/amplified solid tumour types (except breast cancer, gastric, gastroesophageal junction, or esophageal adenocarcinoma) (Cohort 6)

Patients with mutated HER2 (without overexpression/amplification) will be enrolled into one of four cohorts:

• Urothelial cancer (Cohort 7)
• Breast cancer (Cohort 8)
• Gastroesophageal cancer (Cohort 9)
• Any other HER2-mutated solid tumour types (except non-squamous NSCLC) (Cohort 10)

Exclusion Criteria: 

Preious treatment with any HER2 Tyrosine kinase inhibitors (TKIs)

Substudy status: Recruiting

Registration number: NCT06581432

Title: Brightline-2: A Phase IIa/IIb, Open-label, Single-arm, Multi-centre Trial of BI 907828 for Treatment of Patients With Locally Advanced / Metastatic, MDM2 Amplified, TP53 Wild-type Biliary Tract Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, or Other Selected Solid Tumours

The aim of BRIGHTLINE-2 is to investigate BI 907828 monotherapy in the treatment of MDM2 amplified, TP53 wild-type Biliary Tract Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, Lung Adenocarcinoma and Urothelial Bladder Cancer.

Eligible Population: 

MDM2 amplified (copy number ≥8), TP53 wild-type:

• Cohort 1: (CLOSED) Biliary tract adenocarcinoma (intra and extrahepatic cholangiocarcinoma, gallbladder cancer and ampullary cancer)
• Cohort 2: (CLOSED) Pancreatic Ductal Adenocarcinoma
• Cohort 3: Lung Adenocarcinoma
• Cohort 4: (CLOSED) Urothelial Bladder Cancer

Substudy status: Recruiting

Registration number: NCT05512377

Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation and Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7656594 in Patients With Advanced or Metastatic Prostate Cancer

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of RO7656594 in participants with advanced or metastatic prostate cancer. It will also identify recommended doses and regimens for RO7656594 for subsequent studies.

Eligible Population: 

Eligiblity Criteria: 

• Metastatic prostate adenocarcinoma without small-cell carcinoma or neuroendrocrine features
• Prior therapy with ≥1 second-generation androgen receptor (AR)-targeted therapy (e.g., abiraterone, enzalutamide, apalutamide, darolutamide).
• Prior therapy with ≥1 taxane regimen or are considered ineligible for treatment with a taxane regimen or have refused treatment with a taxane regimen.
• For participants with a known pathogenic breast cancer gene 1 (BRCA1) or BRCA2 mutation: prior therapy with a poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor, or are considered ineligible for treatment with a PARP inhibitor, if such therapy is approved and available.

Substudy status: Recruiting

Registration number: NCT05800665

Title: A Phase Ia/Ib Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 as a Single Agent and in Combination With Other Anti-cancer Therapies in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation

The aim of this study is to evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation.

Eligible Population: 

Patients with histologically documented advanced or metastatic solid tumor with KRAS G12C mutation. 

• Arm A: Participants with select solid tumors.
• Arm B: Participants with non-small cell lung cancer.
• Arm C: Participants with colorectal cancer. 
• Arm D: Participants with solid tumors. 
• Arm E: Participants with non-small cell lung cancer. 
• Arm F: Participants with solid tumors.
• Arm G: Participants with solid tumors.                                                                                                                

Substudy status: Recruiting

Registration number: NCT04449874

Title: A Phase Ia/Ib, Open-Label, Multicenter, Global, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of XmAb24306 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

The aim of the study is to evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 alone or in combination with a checkpoint inhibitor treatment in participants with locally advanced or metastatic solid tumors.

Eligible Population: 

Patients with locally advanced or metastatic solid tumours.

Substudy status: Recruiting

Registration number: NCT04250155

Title: A Phase Ia/Ib, Open Label, Multicenter, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7502175 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

The aim of this study is to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of RO7502175 when administered as a single agent and in combination with atezolizumab in adult participants with locally advanced or metastatic solid tumors, including non-small-cell lung cancer, head and neck squamous cell carcinoma, melanoma, triple-negative breast cancer, esophageal cancer, gastric cancer, cervical cancer, urothelial carcinoma, clear cell renal cell carcinoma and hepatocellular carcinoma.

Eligible Population: 

Patients with histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy.

Trial is in the Expansion phase and only recruiting for Gastric, Lung, and HNSCC cohorts. 

Substudy status: Recruiting

Registration number: NCT05581004

Title: A Phase Ib, Open-Label, Multicenter Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-Care Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors.

The aim of this study is to evaluate the safety and tolerability of RO7496353 when administered in combination with a checkpoint inhibitor with or without standard-of-care chemotherapy in participants with locally advanced or metastatic solid tumors such as non-small cell lung cancer, gastric cancer and pancreatic ductal adenocarcinoma. The study will be conducted in 2 stages: an initial safety run-in stage and an expansion stage.

Eligible Population: 

Patients with histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy.

• Cohort A: Participants with NSCLC 
• Cohort B: Participants with GC 
• Cohort C: Participants with PDAC 

Substudy status: Recruiting

Registration number: NCT05867121

Title: A Phase 1b Study to Evaluate HMBD-001 in Combination with Docetaxel with or Without Cetuximab in Participants with Advanced Squamous Non-Small Cell Lung Cancers, and HMBD-001 in Combination with Cetuximab in Participants with Advanced Squamous Cell Cancers

This is a phase 1b multi-center, open-label study of HMBD-001 in combination with docetaxel with or without cetuximab in participants with locally advanced or metastatic squamous Non-Small Cell Lung Cancers, and HMBD-001 in combination with cetuximab in participants with advanced Squamous Cell Cancers

Eligible Population: 

Patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) (ArmB), sqNSCLC, HNSCC, ESCC, CSCC , or cervical SCC (ArmC). Patients must have progressed on at least one approved or comparable platinum-based therapy for NSCLC and had prior treatment with a mAb against PD-1 or PD-L1. 

Exclusion criteria: 

Prior treatment with HMBD-001, docetacel, cetuxinab or any other agent that targets EGFR or HER3, inlcuding pan-HER inhibitors. Prior treatment with doxetaxel is allowed for ArmC. 

Substudy status: Recruiting

Registration number: NCT05910827

Title: A Phase Ib Multi-Center, Open-Label Study of HMBD-001 With or Without Chemotherapy in Participants With Advanced Solid Tumors Harboring an NRG1 Gene Fusion or HER3 mutation

The aim of this study is to evaluate HMBD-001 with or without chemotherapy in participants with advanced solid tumors harboring an NRG1 Gene Fusion or HER3 mutation

Eligible Population: 

Cancer harboring an NRG1 gene fusion with EGF-like domain or a HER3 mutation.

• Cohort A: Locally advanced or metastatic pancreatic adenocarcinoma (PDAC) harboring NRG1 gene fusions.
• Cohort B: Locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring NRG1 gene fusions.
• Cohort C: Other solid tumors harboring NRG1 gene fusions and not eligible for Cohort A or B.
• Cohort D: Solid tumors harboring select HER3 ECD mutations and WT in select genes.

Substudy status: Recruiting

Registration number: NCT05919537

Title: Phase 1/2 Open Label, Dose Escalation and Expansion Study of MDNA11, IL-2 Superkine, Administered Alone or in Combination with an Immune Checkpoint Inhibitor in Patients with Advanced Solid Tumors

The aim of this study is to evaluate safety, tolerability, pharmacokinetic properties, pharmacodynamic effects, and preliminary anti-tumor activity of MDNA11 [both as a monotherapy and in combination with checkpoint inhibitor (pembrolizumab)] in patients with selected advanced solid tumors.

Eligible Population: 

• Histologically confirmed diagnosis of locally advanced unresectable or metastatic MSI-H or dMMR solid tumor. N.B. enrolment of MSI-H colorectal cancer may be limited by the Sponsor (e.g. up to ~50% of patients) to ensure representation of other MSI-H indications.
• Confirmed dMMR (mismatch repair deficient) or MSI-H (microsatellite instability-high) status: dMMR/MSI-H status diagnosis via IHC (e.g. complete loss of nuclear immunoreactivity of at least 2 of the mismatch repair genes: MSH2, MSH6, MLH1 and PMS2), NGS or PCR based tests.
• Disease progression within 3 months of treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.
• PD-1 treatment progression is defined by meeting all the following criteria:
  a. Has received at least 2 doses (i.e. exposure for at least 6 weeks) of an approved anti-PD-1/L1 mAb.
  N.B. Checkpoint inhibitor naive patients who do not have access to anti-PD-1/L1 mAb for their tumor (e.g. not approved or not locally available in the country of planned enrolment) may be eligible for enrolment.
  b. Initial evidence of PD and where possible, confirmed by a second assessment (i.e. scan no less than four weeks from the date of the first/initial documented PD).
  c. Anti-PD-1/L1 therapy (whether monotherapy or combination), where available, is not required to be the most recent systemic anti-tumor therapy received prior to enrolment.
  N.B. Documentation should include start, stop and progression dates of anti-PD-1/L1 therapy and any other checkpoint inhibitor.

Substudy status: Recruiting

Registration number: NCT05086692

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)
• 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 Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

This is a Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation.  

Eligible Population: 

Eligibility Critera: 

• Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy with any mutation of SMARCA4 by local testing that has either progressed on or is ineligible for standard of care therapy

Exclusion Criteria: 

• Participants with solid tumors with known concomitant SMARCA2 mutation or loss of protein expression
• Receipt of any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4).

Substudy status: Recruiting

Registration number: NCT06560645

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.

Eligible Population: 

Only 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)

Substudy status: Recruiting

Registration number: NCT04802759

Title: A Phase III Randomized, Open-Label Study Evaluating Efficacy and Safety of Giredestrant Compared With Fulvestrant, Both Combined With a CDK4/6 Inhibitor, in Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer With Resistance to Prior Adjuvant Endocrine Therapy

The aim of this study is to evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.

Eligible Population: 

• Patients with locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent.
• ER positive and HER2 negative tumor, assessed locally on the most recent tumor biopsy (or archived tumor sample).
• Confirmed ESR1 mutation status (ESR1m vs. ESR1nmd) in baseline circulating tumor DNA (ctDNA).
• Resistance to prior adjuvant endocrine therapy (ET).
• No prior systemic anti-cancer therapy for advanced disease.

Substudy status: Recruiting

Registration number: NCT06065748

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 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.

Substudy status: Recruiting

Registration number: NCT05789082

Title: The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic non-small cell lung cancer (NSCLC).

A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Patients With Previously Treated KRAS G12C-Positive Advanced or Metastatic Non-Small Cell Lung Cancer

Eligible Population: 

Inclusion Criteria: 

• Diagnosed NSCLC
• Disease progression on at least one prior systemic therapy but not more than three lines of systemic therapy in metastatic setting
• Documented KRAS G12C mutation

Exclusion Criteria: 

• Mixed small-cell lung cancer or large ell neuroendocrine histology
• Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
• More than 30 Gy of radiotherapy to lung within 6 months of randomization

Substudy status: Recruiting

Registration number: NCT06497556

Title: Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

The aim of TAPISTRY is to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in rational, specified combinations in participants with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations or who are tumor mutational burden (TMB)-high as identified by a validated next-generation sequencing (NGS) assay. Participants with solid tumors will be treated with a drug or drug regimen tailored to their NGS assay results at screening. Participants will be assigned to the appropriate cohort based on their genetic alteration(s). 

Eligible Population: 

• Cohort A (CLOSED): ROS1 fusion-positive tumors. Participants with metastatic or advanced solid tumors, with the exception of NSCLC will receive entrectinib.
• Cohort B: NTRK1/2/3 fusion-positive tumors. Participants with metastatic or advanced solid tumors will receive entrectinib.
• Cohort C (CLOSED): ALK fusion-positive tumors. Participants with metastatic or advanced solid tumors, with the exception of NSCLC, will receive alectinib.
• Cohort D (CLOSED): TMB-high tumors. Participants with metastatic or advanced solid tumors will receive atezolizumab.
• Cohort E (CLOSED): AKT1/2/3 mutant-positive tumors. Participants with metastatic or advanced solid tumors will receive ipatasertib.
• Cohort F (CLOSED): HER2 mutant-positive tumors. Participants with metastatic or advanced solid tumors will receive trastuzumab emtansine.
• Cohort G (CLOSED): MDM2-amplified, TP53 wild-type tumors. Participants with metastatic or advanced solid tumors will receive idasanutlin.
• Cohort H (CLOSED): PIK3CA multiple mutant-positive tumors. Participants with metastatic or advanced solid tumors will receive GDC-0077.
• Cohort I (CLOSED): BRAF class II mutant or fusion-positive tumors. Participants with BRAF class II mutant/fusion-positive tumors will receivebelvarafenib.
• Cohort J (CLOSED): BRAF class III mutant-positive tumors . Participants with BRAF class III mutant-positive tumors will receive belvarafenib.
• Cohort K (CLOSED): RET fusion-positive tumors. Participants with RET fusion-positive tumors, with the exception of NSCLC will self-administer Pralsetinib.
• Cohort L (CLOSED): KRAS G12C-positive tumors. Participants with KRAS G12C-positive tumors, with the exception of NSCLC and CRC will self-administer GDC-6036.
• Cohort M (CLOSED): ATM Loss of Function tumors. Participants with ATM Loss of Function tumors will self-administer Camonsertib.
• Cohort N (CLOSED): SETD2 Loss of Function tumors. Participants with SETD2 Loss of Function tumors will self-administer Camonsertib.

Substudy status: Recruiting

Registration number: NCT04589845

Title: A Phase II, Randomized, Multicenter, Open-Label, Controlled Study of RO7247669 Alone or in Combination With Tiragolumab Versus Atezolizumab in Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer Who Are Ineligible for Platinum-Containing Chemotherapy

The aim of this study is to evaluate the efficacy, safety, and pharmacokinetics alone or in combination with tiragolumab compared with atezolizumab in participants with previously untreated, locally advanced or metastatic urothelial cancer (mUC) who are ineligible to receive a platinum containing chemotherapy.

Eligible Population: 

• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Participants with squamous, sarcomatoid, micropapillary, and glandular variant histologies are eligible for inclusion in the study, provided that a urothelial component is present in the tumor specimen.
• Ineligible ("unfit") to receive platinum-based chemotherapy.
• No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma (UC).

Substudy status: Recruiting

Registration number: NCT05645692

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).
• 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).
• 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).
• 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).

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 or 1 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)

Substudy status: Recruiting

Registration number: NCT06127407

Title: A Phase 1, Open-label, Multicenter Clinical Trial of S095035 (MAT2A Inhibitor) in Adult Participants With Advanced or Metastatic Solid Tumors With Homozygous Deletion of MTAP

This is a first-in-human Phase 1, multicenter, open-label dose escalation study of S095035 in adult participants with advanced or metastatic solid tumors with homozygous deletion of MTAP who have failed to respond to or have progressed after at least 1 prior treatment regimen, and for whom additional effective standard treatment is not available. S095035 is an oral methionine adenosyltransferase 2A [MAT2A] inhibitor.   

Eligible Population: 

• Advanced or metastatic solid tumors (excluding central nervous system tumors) that have progressed despite at least one prior treatment regimen given for advanced/metastatic disease, and for whom additional effective standard therapy is not available.
• MTAP homozygous deletion in tumor tissue, determined using NGS.
• Participants willing to undergo paired fresh biopsy (pre-treatment and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns. 
• Participants who have already received a MAT2A or PRMT5 (protein arginine methyltransferase 5) inhibitor are excluded.

Substudy status: Recruiting

Registration number: NCT06188702