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 BTC (Part 1e)
• MTAP-null HNSCC (Part 1f)`
• MTAP-null Pancreatic adenocarcinoma (Part 1g)

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: 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: An Open Label, Phase I Dose Escalation Trial, With Dose Confirmation and Expansion, of BI 1810631 as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations

The aim of this trial is to investigate BI 1810631 in the treatment of NSCLC patients with HER2 mutations.

Eligible Population: 

Phase Ib - Dose expansion part:

• Cohort 1 (CLOSED): Non-squamous NSCLC HER2 TKD mutation-positive who have received, in the advanced/metastatic setting, at least one line of systemic therapy.
• Cohort 2: Non-squamous NSCLC HER2 TKD mutation-positive who are treatment naïve (no prior systemic therapy including chemotherapy, immunotherapy or targeted therapy for stage IIIB and IV adenocarcinoma). Neo or adjuvant chemotherapy, chemoradio or radiotherapy is permitted if at least 6 months has elapsed prior to disease progression.
• Cohort 3: NSCLC HER2 mutation outside the TKD and has received in the advanced/metastatic setting, at least one line of systemic therapy that includes a platinum-based combination chemotherapy.
• Cohort 4 (LIMITED SLOTS): NSCLC HER2 TKD mutation-positive with active brain metastases previously treated or treatment naive.
• Cohort 5 (CLOSED): Non-squamous NSCLC HER2 TKD mutation-positive previously treated with HER2 directed antibody-drug conjugate (ADC) therapies.

Substudy status: Recruiting

Registration number: NCT04886804

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

Substudy status: Recruiting

Registration number: NCT05512377

Title: Brightline-4: A Phase III Open-label, Single-arm, Multi-center Study to Assess the Safety and Efficacy of Brigimadlin (BI 907828) Treatment in Patients With Treatment-naïve or Pre-treated Advanced Dedifferentiated Liposarcoma

This study is open to adults with a type of cancer called dedifferentiated liposarcoma (DDLPS). They can join the study if their tumours are positive for MDM2. The purpose of this study is to find out whether a medicine called brigimadlin (BI 907828) is tolerated by and helps people with DDLPS. Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         

Eligible Population: 

• Locally advanced or metastatic, unresectable, progressive or recurrent Dedifferentiated liposarcoma (DDLPS), meeting the criteria for an open study cohort:

Cohort A: patient has not received prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)

Cohort B: patient has received any prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)                 

• DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by FISH or NGS.
• ECOG 0 OR 1.   
• TP53 gene (screening for TP53 status is not required)  
• Previous administration of brigimadlin or any other MDM2-p53 or MDM4 regulator of p53 (MDM4/MDMX)-p53 antagonist 
• Previous treatment in study 1403-0008 (Brightline-1).

Substudy status: Recruiting

Registration number: NCT06058793

Title: A Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Patients With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Patients With Metastatic Colorectal Cancer

The aim of this study is to evaluate the safety of GDC-1971 in combination with either osimertinib or cetuximab. 

Eligible Population: 

Participants with unresectable, locally advanced or metastatic NSCLC that has progressed on/after prior treatment with third-generation epidermal growth factor receptor inhibitor OR participants with metastatic CRC that has progressed on/after prior treatment with an EGFR inhibitor.

• Positive for an EGFR exon 19 deletion or exon 21 L858R mutation. 
• Negative for acquired on-target EGFR alterations for Colorectal Cancer Cohorts.
• Negative for kirsten rat sarcoma viral oncogene homolog (KRAS) alterations.
• Negative for neuroblastoma RAS viral oncogene homolog (NRAS) alterations.
• Negative for proto-oncogene B-Raf (BRAF) V600E alterations.

Substudy status: Recruiting

Registration number: NCT05954871

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.

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 Ib, Open-Label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-Mutant Advanced Melanoma Who Have Received Anti-PD-1/PD-L1 Therapy

The aim of this study to evaluate the safety, pharmacokinetics, and activity of belvarafenib as a single agent and in combination with either cobimetinib or cobimetinib plus nivolumab in patients with NRAS-mutant advanced melanoma who have received anti-PD-1/PD-L1 therapy.

Eligible Population: 

• Histologically confirmed, metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage III) cutaneous melanoma, that has progressed on or after treatment with anti-PD-1 or anti-PD-L1 therapy.
• Treatment with anti-PD-1/PD-L1 in the adjuvant setting is acceptable, patients must have progressed disease.
• Documentation of NRAS mutation-positive within 5 years prior to screening.

Substudy status: Recruiting

Registration number: NCT04835805

Title: A Phase Ib, Open-Label Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

The aim of this study is to evaluate the safety, pharmacokinetics (PK), and activity of GDC-1971 when administered in combination with atezolizumab in participants with locally advanced or metastatic solid tumors.

Eligible Population: 

Dose-Finding Stage:

• Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable.

Expansion Stage:

• NSCLC Cohort: Histologically confirmed locally advanced or metastatic NSCLC. Absence of EGFR and ALK. PD- L1 positive.
• HNSCC Cohort: Histologically confirmed recurrent, or metastatic HNSCC. PD-L1 positive. 
• BRAF WT melanoma Cohort: Histologically confirmed locally advanced or metastatic or unresectable locally advanced cutaneous BRAF WT melanoma or melanomas of unknown primary that are non-mucosal and non -uveal that has progressed on or after treatment that included anti PD1 or anti PD-L1 therapy. 
• Other Advanced or Metastatic Solid Tumors Cohort: Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable, standard therapy is considered inappropriate, or an investigational agent is a recognized standard of care.

Substudy status: Recruiting

Registration number: NCT05487235

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: A Phase Ib Multi-Centre, Open-Label Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers

The aim of this study is to evaluate HMBD-001 in combination with docetaxel with or without cetuximab in participants with locally advanced or metastatic squamous Non-Small Cell Lung Cancers.

Eligible Population: 

Patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC). 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. 

Substudy status: Recruiting

Registration number: NCT05910827

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: Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)

This study aims to evaluate the efficacy and safety of belzutifan monotherapy in participants with Advanced Gastrointestinal Stromal Tumor (wt GIST), or Advanced Solid Tumors With hypoxia inducible factor-2 alpha (HIF-2α) related genetic alterations.

Eligible Population: 

• Cohort C: GIST wt cohort: Locally advanced or metastatic GIST with the absence of sensitizing mutations in both platelet derived growth factor receptor alpha (PDGFRA) and receptor tyrosine kinase (c-KIT).
• Cohort D: HIF-2α related genetic alteration cohort: Locally advanced or metastatic solid tumor that have progessed on standard therapy with germline or somatic mutations in at least one of the HIF-2α related genes (HIF-2α/EPAS1, FH, SDHA, SDHB, SDHC, SDHD, SDHAF2, EGLN1, EGLN@, MDH2, ELOC/TCEB1).

Substudy status: Recruiting

Registration number: NCT04924075

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: 

• Advanced solid malignancy with a TP53 Y220C mutation
• ECOG 0 or 1
• Previously treated with one or more lines of anticancer therapy and progressive disease
• Additional Criteria for Inclusion in Phase 1b: Anti-PD-1/PD-L1 naive or must have progressed on treatment
• Primary CNS tumors not eligible
• Additional Criteria for Exclusion from Phase 1b (PC14586 in combination with pembrolizumab): Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE)
• Additional Criteria for Exclusion from Phase 2 (PC14586 monotherapy): Known KRAS mutation

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 1) focus on participants with inoperable, locally advanced or metastatic, estrogen receptor (ER) positive, HER2 negative breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor in the first- or second-line setting.

Eligible Population: 

Cohort 1 (Stage 1 [and Stage 2, only where indicated]):

• Documented estrogen receptor positive (ER+) tumor.
• Patients for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines.
• Radiologic/objective evidence of recurrence or progression after the most recent systemic therapy for breast cancer.
• Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease (note: at least one line of therapy must have contained a CDK4/6i administered for a minimum of 8 weeks prior to disease progression).
• Prior fulvestrant therapy is allowed.

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 Phase III, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Versus Alpelisib Plus Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Who Progressed During or After CDK4/6 Inhibitor and Endocrine Combination Therapy

The aim of this study is to evaluate the efficacy and safety of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after cyclin dependent kinase 4/6i (CDK4/6i)-based therapy.

Eligible Population: 

• Locally advanced or metastatic breast cancer.
• Disease progression during or after CDK4/6i and endocrine combination therapy.
• Up to 2 lines of prior treatment in metastatic setting.
• HR-positive and HER2-negative tumor.
• Detection of specified PIK3CA mutation.

Substudy status: Recruiting

Registration number: NCT05646862

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: A Randomized Open Label Phase II Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma

The aim of this study to evaluate the efficacy, safety, and pharmacokinetics of RO7247669 in combination with axitinib alone or with tiragolumab (anti-TIGIT) and axitinib, as compared to pembrolizumab and axitinib in participants with previously untreated, unresectable locally advanced or metastatic clear-cell renal cell carcinoma (ccRCC).

Eligible Population: 

Histologically confirmed ccRCC with or without sarcomatoid features.

Substudy status: Recruiting

Registration number: NCT05805501

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 Immunotherapy-Based Treatment Combinations In Patients With Metastatic Non-Small Cell Lung Cancer

The aim of this study is to evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC).

Eligible Population: 

• Histologically or cytologically confirmed metastatic, non-squamous or squamous Non-Small Cell Lung Cancer (NSCLC).
• Cohort 1: Patients with high tumour PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC.
• Cohort 2: Patients who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression.

Substudy status: Recruiting

Registration number: NCT03337698

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 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 A: (CLOSED) Inavolisib + Cetuximab (PIK3CA altered tumors, no RAS (KRAS, NRAS) mutation or BRAFV600E mutation detected).
• Cohort C (CLOSED): Atezolizumab + tiragolumab +/- bevacizumab (MSI-H tumors).
• Cohort E: Divarasib (GDC-6036) + cetuximab + FOLFOX (KRAS G12C altered tumors).
• Cohort F: Divarasib (GDC-6036) + cetuximab + FOLFIRI (KRAS G12C altered tumors).

Substudy status: Recruiting

Registration number: NCT04929223

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: 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: 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 (PAUSED, reopen planned early 2024): 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*: 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: An Open-Label Early Access Phase IIIb study to provide patients with a pretreated locally advanced or metastatic cholangiocarcinoma harbouring an IDH1 mutation with access to the IDH1 inhibitor Ivosidenib

The aim of this Phase IIIb research study is to consolidate the data that ivosidenib is safe and effective in adult patients with previously treated, locally advanced, or metastatic cholangiocarcinoma (CCA).

Eligible Population: 

• Pretreated locally advanced or metastatic cholangiocarcinoma harbouring one of the following IDH1 mutations: IDH1 R132C, R132L, R132G, R132H, or R132S.
• Must not have received prior treatment with an IDH1 inhibitor. 

Substudy status: Recruiting

Registration number: NCT05876754

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