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: 

• Evidence of homozygous loss of CDKN2A (null) (Parts 1a, 1j, 1k, and 2a only) and/or MTAP (null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
• Metastatic or locally advanced solid tumor not amenable to curative treatment with surgery and/or radiation.

Substudy status: Recruiting

Registration number: NCT05094336

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: 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: NSCLC HER2 TKD mutation-positive with active brain metastatse previously treated or treatment naive.
• Cohort 5: 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: 

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

Substudy status: Recruiting

Registration number: NCT05512377

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 I, Open-Label, Dose-Escalation Study Of The Safety And Pharmacokinetics Of BLYG8824A Administered Intravenously In Patients With Locally Advanced Or Metastatic Colorectal Cancer

The aim of this study is to evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will make a preliminary assessment of the anti-tumor activity of BLYG8824A in patients with locally advanced or metastatic colorectal cancer.

Eligible Population: 

Incurable, unresectable, locally advanced or metastatic CRC previously treated with multimodality therapy or mCRC.

Substudy status: Recruiting

Registration number: NCT04468607

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 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 NRG1 Gene Fusions

The aim of this study is to evaluate HMBD-001 with or without chemotherapy in participants with advanced solid tumors harboring NRG1 gene fusions.

Eligible Population: 

Cancer harboring an NRG1 gene fusion with EGF-like domain.

• 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) with the following genomic signature:

• KRAS/PIK3CA/BRAF: absence of gain of function single nucleotide variants (SNVs) and insertions/deletions (INDELs). 
• PTEN: absence of loss of function SNVs and INDELs and homozygous loss. 
• MET: absence of amplification (copy number > 6). 

Substudy status: Recruiting

Registration number: NCT05910827

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: An Open-label, Multicenter, Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RO7428731 in Participants With Glioblastoma Expressing Mutant Epidermal Growth Factor Receptor Variant III

The aim of this study is to assess safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy of RO7428731 administered as a monotherapy in participants with newly diagnosed or recurrent epidermal growth factor receptor variant III (EGFRvIII)-positive glioblastoma (GBM).

Eligible Population: 

• Patients diagnosed with GBM based on WHO classification of CNS tumors (5th edition).
• Confirmed EGFRvIII expression.

Substudy status: Recruiting

Registration number: NCT05187624

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 II, Open-Label, Multicenter, Platform Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors

The aim of this study is to evaluate the efficacy and safety of multiple biomarker-selected treatments in patients with persistent or recurrent rare epithelial ovarian, fallopian tube, or primary peritoneal tumors.

Eligible Population: 

Patients with persistent or recurrent EOC that meets the following criteria: Histologically confirmed non-high-grade serous, non-high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, including but not limited to low-grade serous ovarian carcinoma, clear cell carcinoma, mucinous carcinoma, carcinosarcoma, undifferentiated carcinoma, seromucinous carcinoma, malignant Brenner tumors, Grades 1 or 2 endometrioid carcinoma, mesonephric-like adenocarcinoma and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). 

• Patasertib + paclitaxel arm (CLOSED): PIK3CA/AKT1/PTEN-altered tumors.
• Cobimetinib arm (CLOSED): BRAF/NRAS/KRAS/NF1-altered tumors.
• T-DM1 arm (CLOSED): ERBB2-amplified/mutant tumors.
• Atezolizumab + bevacizumab arm (CLOSED): Non-matched.
• Giredestrant + abemaciclib arm (CLOSED): ER+ tumors.
• Inavolisib + palbociclib arm: PIK3CA-altered tumors.
• Inavolisib + palbociclib + letrozole arm: ER+ and PIK3CA-altered tumors.
• Inavolisib + olaparib arm (CLOSED): Non-matched.

Substudy status: Recruiting

Registration number: NCT04931342

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 II, Randomized, Multicenter, Double-Blind, Controlled Study of Tobemstomig Plus Platinum-Based Chemotherapy Versus Pembrolizumab Plus Platinum-Based Chemotherapy in Patients With Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

The aim of this study is to evaluate the efficacy, safety, and pharmacokinetics of tobemstomig  in combination with platinum-based chemotherapy compared with pembrolizumab plus platinum-based chemotherapy in participants with previously untreated, locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) non-small-cell lung cancer (NSCLC) who are not eligible to receive curative surgery and/or definitive chemoradiotherapy.

Eligible Population: 

• Histologically or cytologically documented locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC who are not eligible for curative surgery and/or definitive chemoradiotherapy.
• No prior systemic treatment for metastatic NSCLC.
• Known tumor PD-L1 status.
• NSCLC known to have a mutation in the EGFR gene or an ALK fusion oncogene is not eligible.

Substudy status: Recruiting

Registration number: NCT05775289

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).
• Cohort C: Atezolizumab + tiragolumab +/- bevacizumab (MSI-H tumors).
• Cohort E (PLANNED, late 2023): Divarasib (GDC-6036) + cetuximab + FOLFOX (KRAS G12C altered tumors).
• Cohort F (PLANNED, late 2023): Divarasib (GDC-6036) + cetuximab + FOLFOX (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: RET fusion-positive tumors. Participants with RET fusion-positive tumors will self-administer Pralsetinib.

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