News - MSI-H/dMMR - LARVOL VERI

PIK3CA mutations in endometrial cancer: a pre-planned biomarker analysis from the phase II MITO END-3 study of carboplatin and paclitaxel with or without avelumab in advanced or recurrent endometrial cancer (AIOM 2024)

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

1 day ago

P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PIK3CA H1047R • PTEN mutation • ARID1A mutation • POLE mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + PTEN mutation • PIK3CA C420R • PIK3CA E545A • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546R

FoundationOne® CDx

carboplatin • paclitaxel • Bavencio (avelumab)

Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)

Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.

1 day ago

Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases

TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

TMB-H • MSI-H/dMMR

TruSight Oncology 500 Assay

oxaliplatin • irinotecan

Negative hyperselection and mechanisms of acquired resistance to first-line chemotherapy plus anti-EGFR in pMMR RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts): a translational analysis of the TRIPLETE trial (AIOM 2024)

TRIPLETE is a phase III trial where 435 pts with RAS/BRAF wt – per local assessment – mCRC were randomized to receive first-line FOLFOX/ panitumumab (pan) or mFOLFOXIRI/pan... In contrast to previous data, negative hyperselection both through tissue and plasma analysis failed to demonstrate a prognostic role among pMMR RAS/BRAF wt mCRC pts treated with first-line chemotherapy plus pan. The confounding effect of the associated chemotherapy is a potential explanation for this finding. Tissue and plasma analyses at baseline failed to provide fully concordant results.

1 day ago

Clinical • Preclinical • Metastases

BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

BRAF V600E • MSI-H/dMMR • BRAF V600 • BRAF wild-type • RAS mutation • RAS wild-type

FoundationOne® CDx • Oncomine™ Pan-Cancer Cell-Free Assay • Oncomine Focus Assay

5-fluorouracil • Vectibix (panitumumab) • leucovorin calcium

More subtle microsatellite instability better predicts fluorouracil insensitivity in colorectal cancer patients. (PubMed, Sci Rep)

In Type A MSI+ tumours, the patient response to fluoropyrimidine and oxaliplatin was significantly poor (Fisher's exact test, p = 0.021)...Type A MSI was an independent predictor of patient prognosis in this pilot cohort (Cox regression analysis, p = 0.003). Thus, more subtle Type A MSI better predicts fluoropyrimidine insensitivity in colorectal cancer patients, which may shed light on a hitherto overlooked connection between the MSI phenotypes and drug resistance in human cancer.

2 days ago

Journal • Microsatellite instability • MSi-H Biomarker

MSI (Microsatellite instability)

MSI-H/dMMR

5-fluorouracil • oxaliplatin • leucovorin calcium

Total neoadjuvant therapy involving checkpoint inhibitors in locally advanced MSI/dMMR rectal cancer - a case report. (PubMed, Klin Onkol)

This case highlights the importance of molecular testing in rectal cancer, which should be performed in all advanced cases requiring more intensive oncologic therapy than surgery alone. MSI/dMMR status indicates the need for a specific approach that may significantly improve the outcomes of these patients.

2 days ago

Journal • Checkpoint inhibition • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR

Redefining pancreatic cancer management with tumor-agnostic precision medicine. (PubMed, Carcinogenesis)

Despite the rarity of NTRK fusions in pancreatic cancer, larotrectinib and entrectinib have exhibited effectiveness in NTRK fusion-positive pancreatic cancers. Additionally, repotrectinib, a next-generation NTRK inhibitor, has shown promising activity in NTRK positive pancreatic cancer patients who have developed acquired resistance to previous NTRK inhibitors. Immune checkpoint inhibitors, such as pembrolizumab and dostarlimab, have proven to be effective in dMMR/MSI-H pancreatic cancers...It is crucial to continue implementing comprehensive screening strategies that encompass the ability to detect all these tumor-agnostic biomarkers. This will be essential in identifying pancreatic cancer patients who may benefit from these therapies.

3 days ago

Journal • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Pan tumor

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)

TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • KRAS G12C • HER-2 overexpression • BRAF mutation • BRAF V600 • RET fusion • FGFR2 mutation • FGFR2 fusion • ALK fusion • NRG1 fusion • KRAS G12 • NTRK positive • NTRK fusion

Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Jemperli (dostarlimab-gxly) • Augtyro (repotrectinib)

Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer. (PubMed, Gynecol Oncol)

We demonstrated that ER/PR expression remain prognostically relevant within the molecular subgroups, and that a three-tiered cutoff refines prognostication. These data support incorporating routine evaluation of ER/PR expression in clinical practice.

3 days ago

Journal

ER (Estrogen receptor) • PGR (Progesterone receptor)

MSI-H/dMMR • TP53 expression • PGR expression

RePERSO: Evaluation of Treatment PERSOnalization Based on Its Therapeutic Monitoring in Patients with Metastatic Colorectal Cancer Treated with REgorafenib (clinicaltrials.gov)

P4, N=110, Active, not recruiting, Rennes University Hospital | Trial primary completion date: Sep 2024 --> Jun 2025

3 days ago

Trial primary completion date • Metastases

BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)

BRAF V600E • MSI-H/dMMR • BRAF V600 • RAS wild-type

Stivarga (regorafenib)

KEYNOTE-E64: Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067 (clinicaltrials.gov)

P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

3 days ago

Enrollment open • Trial completion date • Trial primary completion date • Combination therapy • Metastases

ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)

TMB-H • MSI-H/dMMR • ALK positive • ALK mutation

Keytruda (pembrolizumab) • Gazyva (obinutuzumab) • vevoctadekin (ST-067)

Iparomlimab (QL1604) in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) unresectable or metastatic solid tumors: a pivotal, single-arm, multicenter, phase II trial. (PubMed, J Hematol Oncol)

No iparomlimab-related death occurred. Iparomlimab presented encouraging antitumor activity with durable response and tolerable safety profile.Trial registration ClinicalTrials.gov Identifier: NCT04326829.

3 days ago

P2 data • Journal • Mismatch repair • Microsatellite instability • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR

iparomlimab (QL1604)

Case report: MSI-H, EGFR mutation, and ground-glass nodules as diffuse pulmonary hematogenous metastases. (PubMed, Front Immunol)

Here, we report a case of a lung adenocarcinoma patient presenting with ground-glass metastases, MSI-H, and EGFR-sensitive mutation and provide clinical data on the efficacy and prognosis. We describe the predictive significance of carcinoembryonic antigen (CEA) for disease progression when there is inconsistency between treatment effectiveness and CEA changes.

3 days ago

MSi-H Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • MSI (Microsatellite instability) • CEACAM5 (CEA Cell Adhesion Molecule 5)

EGFR mutation • MSI-H/dMMR

A phase II study of induction PD-1 blockade (nivolumab) in patients with surgically completely resectable mismatch repair deficient endometrial cancer (NIVEC). (PubMed, J Gynecol Oncol)

Correlative studies include genomic characterization of tumors, assessment of immune infiltration of tumor microenvironment, and serial circulating cell-free DNA and immune biomarkers. ClinicalTrials.gov Identifier: NCT05795244.

3 days ago

P2 data • Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker

MSI (Microsatellite instability)

MSI-H/dMMR

Opdivo (nivolumab)

Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer. (PubMed, Oncologist)

Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.

3 days ago

Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker

BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43)

BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation

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Efficacy and safety of dostarlimab in combination with chemotherapy in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in a phase 3, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). (PubMed, Gynecol Oncol)

All primary and secondary efficacy assessments demonstrate the consistent benefit of dostarlimab plus carboplatin-paclitaxel. The improvements seen in survival and the manageable safety profile support the favorable benefit-risk profile for dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H primary advanced or recurrent EC.

3 days ago

P3 data • Journal • Combination therapy • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR

carboplatin • paclitaxel • Jemperli (dostarlimab-gxly)

Performance of Idylla MSI and Promega LMR Assays for Pan-Cancer Testing of Microsatellite Instability at Temple University Health System (AMP 2024)

Both assays showed comparable sensitivity in establishing MSI status for CRC and the expanded spectrum of non-CRC tumors. Advantages such as increased number of LMR loci in the Promega assay and the need for only tumor specimen in the Idylla assay increase the utility of these assays in determination of MSI status in a variety of cancers.

5 days ago

Microsatellite instability • MSi-H Biomarker • Pan tumor

MSI (Microsatellite instability)

MSI-H/dMMR

Idylla™ MSI Test

Evaluation of Promega OncoMate MSI Dx Analysis System in Colorectal Cancer, Endometrial Cancer, and Sebaceous Neoplasms (AMP 2024)

The research study demonstrated the effectiveness of the Promega OncoMate MSI Dx Analysis System in detecting MSI in colorectal cancer, endometrial cancer, and sebaceous neoplasms in comparison with MMR IHC. The correlation for CRC was excellent, and EC and SN showed good correlation, though further investigation into discordant samples is necessary. This research study indicates that the OncoMate MSI Dx test offers excellent clinical utility in the diagnosis and management of LS in CRC, and can provide additional insights into EC and SN sample MSI status for LS and MTS research.

5 days ago

MSi-H Biomarker

MSI (Microsatellite instability)

MSI-H/dMMR

OncoMate™ MSI

Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)

Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.

5 days ago

Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion

OncoExTra™ test

Analytical Validation of the Promega Long Mononucleotide Repeat Microsatellite Instability Assay (AMP 2024)

Via the analysis of longer homopolymer repeat regions, the Promega LMR MSI assay demonstrates enhanced sensitivity for subtle phenotypes. This assay may be better suited than other PCR- and CE-based approaches for certain disease types.

5 days ago

Microsatellite instability • MSi-H Biomarker • IO biomarker

MSI (Microsatellite instability)

MSI-H/dMMR

Idylla™ MSI Test

Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers (clinicaltrials.gov)

P2, N=35, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

5 days ago

Trial completion

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSI-H/dMMR

Keytruda (pembrolizumab)

SEAMARK: A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer (clinicaltrials.gov)

P2, N=101, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

5 days ago

Enrollment closed

BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)

BRAF V600E • MSI-H/dMMR • BRAF V600

Keytruda (pembrolizumab) • Erbitux (cetuximab) • Braftovi (encorafenib)

Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery (clinicaltrials.gov)

P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | N=31 --> 62 | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

6 days ago

Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition • Mismatch repair • Surgery • Checkpoint block • Metastases

MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSI-H/dMMR • POLE mutation

Jemperli (dostarlimab-gxly)

Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies (clinicaltrials.gov)

P1/2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=12 --> 19

6 days ago

Enrollment closed • Enrollment change • Combination therapy • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR

Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • Imfinzi (durvalumab) • Bavencio (avelumab) • plinabulin (BPI 2358)

Study Evaluating Treatment of Sacituzumab-govitecan for Patients With Metastatic Esophagogastric Adenocarcinoma (clinicaltrials.gov)

P1/2, N=56, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting

6 days ago

Enrollment closed • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR

Trodelvy (sacituzumab govitecan-hziy)

A Phase 1/2 Study to Evaluate the Safety and Efficacy of MK-2870 Monotherapy or in Combination With Other Anticancer Agents in Gastrointestinal Cancers (ChiCTR2400089007)

P2, N=130, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of

8 days ago

New P2 trial • Combination therapy

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • CD4 (CD4 Molecule)

MSI-H/dMMR • BRCA mutation • MSH6 expression

FoundationOne® CDx

5-fluorouracil • sacituzumab tirumotecan (MK-2870)

10d

Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders (clinicaltrials.gov)

P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

10 days ago

Trial completion date • Trial primary completion date • Metastases

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CEACAM5 (CEA Cell Adhesion Molecule 5)

MSI-H/dMMR

Keytruda (pembrolizumab) • Opdivo (nivolumab)

11d

A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of RO7589831 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (clinicaltrials.gov)

P1, N=295, Recruiting, Hoffmann-La Roche | N=220 --> 295

11 days ago

Enrollment change • Combination therapy • Mismatch repair • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR

Keytruda (pembrolizumab)

12d

LYL845-101: A Study to Investigate LYL845 in Adults With Solid Tumors (clinicaltrials.gov)

P1, N=108, Active, not recruiting, Lyell Immunopharma, Inc. | Recruiting --> Active, not recruiting

12 days ago

Enrollment closed • Metastases

BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)

MSI-H/dMMR • BRAF mutation

LYL845

12d

Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel. (PubMed, J Surg Oncol)

Our panel can classify ECs into four subgroups through a simplified process and can be implemented reflexively in clinical practice.

12 days ago

Journal

TP53 (Tumor protein P53) • MLH1 (MutL homolog 1)

TP53 mutation • MSI-H/dMMR

12d

Role of CD47 gene expression in colorectal cancer: a comprehensive molecular profiling study. (PubMed, J Immunother Cancer)

CD47 expression in CRC was associated with the activation of several oncogenic pathways and an immune-engaged TME. Our findings may provide valuable information for considering new therapeutic strategies targeting innate immune checkpoints in CRC.

12 days ago

Journal • MSi-H Biomarker • IO biomarker

MSI (Microsatellite instability) • CD47 (CD47 Molecule)

MSI-H/dMMR • CD47 expression

12d

KRAS mutations in endometrial cancers: Possible prognostic and treatment implications. (PubMed, Gynecol Oncol)

KRAS-mut represents a genotypically distinct group of ECs. Overlap exists with genomic predictors (TMB-high, MSI-high) of immunotherapy response, suggesting a possible biomarker-driven combination option with immunotherapy. Clinical trials to evaluate these strategies should be developed.

12 days ago

Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability)

KRAS mutation • BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS overexpression • HER-2 positive + RAS wild-type

14d

A Study to Investigate Ompenaclid Combined With FOLFIRI Plus Bevacizumab in Advanced/Metastatic Colorectal Cancer (clinicaltrials.gov)

P2, N=70, Active, not recruiting, Inspirna, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Aug 2028 --> Dec 2026 | Trial primary completion date: Aug 2026 --> Sep 2025

14 days ago

Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR • RAS mutation

Avastin (bevacizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • ompenaclid (RGX-202)

14d

DESTINY-CRC02: Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer (clinicaltrials.gov)

P2, N=122, Completed, Daiichi Sankyo | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Oct 2024

14 days ago

Trial completion • Trial completion date

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)

MSI-H/dMMR • HER-2 overexpression • BRAF wild-type • RAS wild-type • HER-2 positive + RAS wild-type

Enhertu (fam-trastuzumab deruxtecan-nxki)

15d

Recapitulating the adenoma-carcinoma sequence by selection of four spontaneous oncogenic mutations in mismatch-repair-deficient human colon organoids. (PubMed, Nat Cancer)

Here, we demonstrate that long-term culture of mismatch-repair-deficient organoids allows the selection of spontaneous oncogenic mutations through the sequential withdrawal of Wnt agonists, epidermal growth factor (EGF) agonists and the bone morphogenetic protein (BMP) antagonist Noggin, while TP53 mutations were selected through the addition of Nutlin-3...Quadruple-pathway (Wnt, EGF receptor, p53 and BMP) mutant organoids formed solid tumors upon xenotransplantation. This demonstrates that carcinogenesis can be recapitulated in a DNA repair-mutant background through in vitro selection that targets four consecutive cancer pathways.

15 days ago

Journal • Mismatch repair

NRAS (Neuroblastoma RAS viral oncogene homolog) • ACVR2A (Activin A Receptor Type 2A)

TP53 mutation • MSI-H/dMMR

Nutlin-3

17d

Spatial context of immune checkpoints as predictors of overall survival in patients with resectable colorectal cancer independent of standard TNM stages. (PubMed, Cancer Res Commun)

We found that the spatial context of PD-1 and TIM-3 successfully predicted the overall survival of CRC patients independent of TNM stage. Dual targeting of PD-1 and TIM-3 in mouse tumor models inhibited tumor progression and reduced T-cell exhaustion, indicating a potential strategy for improving the clinical treatment of CRC.

17 days ago

Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

MSI (Microsatellite instability) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2)

MSI-H/dMMR • PD-1 expression • HAVCR2 expression

17d

Oncogenic Alterations, Race, and Survival in US Veterans with Metastatic Prostate Cancer Undergoing Somatic Tumor Next Generation Sequencing. (PubMed, bioRxiv)

In the equal access VA healthcare setting, Veterans undergoing NGS for mPCa exhibited differences in alteration frequencies in both actionable and non-actionable pathways that may be associated with survival. This analysis affirms the utility of genomic testing for identifying candidates irrespective of race/ethnicity for precision oncology treatments, which could contribute to equitable outcomes in patients with mPCa.

17 days ago

Journal • Next-generation sequencing • MSi-H Biomarker • IO biomarker • Metastases

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • SPOP (Speckle Type BTB/POZ Protein)

MSI-H/dMMR

17d

SPP1+ macrophages and FAP+ fibroblasts promote the progression of pMMR gastric cancer. (PubMed, Sci Rep)

This study uncovered TiME heterogeneity among GC patients with different MMR states, highlighting that the pMMR TiME is distinguished by hypoxia, pro-angiogenesis, and ECM remodeling, driven by the presence of GC2 cells, SPP1 + macrophages, FAP + fibroblasts, and E2 endothelial cells. These findings are pivotal for developing targeted immunotherapies for GC patients with pMMR.

17 days ago

Journal

SPP1 (Secreted Phosphoprotein 1) • GPC3 (Glypican 3)

MSI-H/dMMR • GPC3 expression • GPC3 overexpression

17d

MT-8421-001: Study of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types (clinicaltrials.gov)

P1, N=15, Terminated, Molecular Templates, Inc. | Active, not recruiting --> Terminated; Sponsor Termination

17 days ago

Trial termination

PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • PD-1 (Programmed cell death 1)

MSI-H/dMMR

Opdivo (nivolumab) • MT-8421

17d

XTX301-01: XTX301 in Patients with Advanced Solid Tumors (clinicaltrials.gov)

P1/2, N=358, Recruiting, Xilio Development, Inc. | Phase classification: P1 --> P1/2 | N=174 --> 358

17 days ago

Phase classification • Enrollment change • Metastases

MSI (Microsatellite instability)

MSI-H/dMMR

XTX301

18d

Microsatellite Instability, Epstein-Barr Virus, p53, and β-Catenin in Early Gastric Cancers: Clinicopathologic Association. (PubMed, In Vivo)

We demonstrated that MSI-H and EBVaGC are strongly associated with clinicopathologic parameters and risk factors in EGCs treated with ESD. Molecular testing of gastric cancers should be considered before ESD for better patient management.

18 days ago

Retrospective data • Journal • Microsatellite instability • MSi-H Biomarker

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • MSI-H/dMMR

18d

Association of ATM and ARID1A in gastric carcinoma. (PubMed, Pathol Res Pract)

ATMlow in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1Alow. ATM mutation was also associated with ARID1A mutations, highlighting the interactions between ATM and ARID1A in GC and suggesting a potential therapeutic target.

18 days ago

Journal • MSi-H Biomarker

MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A)

MSI-H/dMMR • ARID1A mutation • ATM underexpression • ATM expression

19d

Disitamab vedotin combined with apatinib in gastric cancer: A case report and review of literature. (PubMed, World J Clin Oncol)

Despite the unfavorable prognosis associated with advanced GC, the implementation of personalized treatment approaches may still prove beneficial for select patients. In patients with HER2-positive GC with extensive metastatic involvement, the use of the HER2-targeted combination with apatinib has demonstrated the potential to prolong both PFS and overall survival.

19 days ago

Review • Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 positive • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • HER-2 amplification + PD-L1 expression • HER-2 positive + HER-2 overexpression

Opdivo (nivolumab) • Herceptin (trastuzumab) • AiTan (rivoceranib) • Aidixi (disitamab vedotin) • anbenitamab (KN026)

20d

Simplifying Mismatch Repair Deficiency Screening in Endometrial Adenocarcinoma: Immunohistochemistry with Two-Antibody Panel (PMS2 and MSH6). (PubMed, Asian Pac J Cancer Prev)

The simplified two-antibody MMR IHC screening approach using PMS2 and MSH6 showed high concordance with the traditional four-antibody panel. This suggests its potential as an alternative method for reflex MMR status testing in endometrial adenocarcinoma. The implementation of this approach could streamline the diagnostic process, reduce costs, and improve the detection of Lynch syndrome in affected individuals and their families. Further studies with larger cohorts and long-term follow-up are needed to validate these findings and assess the clinical implications of this approach in routine practice.

20 days ago

Retrospective data • Journal • Mismatch repair

MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)

MSI-H/dMMR