Home Transformative Themes at #ASCO2022

What to expect at #ASCO2022?

The 2022 ASCO annual meeting program will offer insights into the latest research in cancer care, practice-changing trends, and incremental improvements and identify several new opportunities hidden in current challenges.

Equitable cancer care through innovation will remain a key theme at ASCO 2022, with several ground-breaking studies on new modalities, targets, and combinations. FutureBridge Oncology consulting team has identified transformative themes that will impact the future. 

Transformative Themes

  1. Antibody Drug Conjugate (ADC) development leads the path
  2. Circulating DNA (ctDNA) adopts the role of a vital & versatile biomarker
  3. T Cell and beyond: Success of cell therapies transitioning in solid tumors

 

1. Antibody Drug Conjugates (ADC) developments lead the path

Recent FDA approval of Enhertu based on results from DESTINY-Breast03 is a validation of the increasing interest, investment, and expected growth of the antibody-drug conjugates (ADCs).  The ASCO 2022 will feature >30 studies including continued development of established ADCs and the first in human studies of new ADCs.

Key presentations to watch include:

Breast cancer

  • Enhertu (HER2 ADC) in HER2-low unresectable and/or metastatic breast cancer (Results of phase III DESTINY-Breast04)
  • MRG002 (HER2 ADC) in HER2-low advanced or metastatic breast cancer.
  • Patritumab deruxtecan (HER3 ADC) in HER3-expressing metastatic breast cancer: (Results from phase 1/2 study)
  • Tucatinib + Enhertu in HER2positive locally advanced or metastatic breast cancer with/ without brain metastases (phase 2, HER2CLIMB-04)
  • Enhertu ± anastrozole as neoadjuvant therapy for HER2-low, HR+ early-stage breast cancer (Phase 2, TRIO-US B-12 TALENT)
  • Enhertu + other anti-cancer agents in advanced/metastatic HER2+ (DESTINY-Breast07 [DB-07]) and HER2-low (DESTINY-Breast08 [DB-08]) breast cancer

NSCLC

  • Patritumab deruxtecan (HER3-ADC) in advanced/metastatic NSCLC without EGFR-activating mutations
  • Patritumab deruxtecan + osimertinib in advanced EGFR-mutated NSCLC (phase 1 study)
  • Enhertu in unresectable, locally advanced, or metastatic NSCLC harboring HER2 exon 19 or 20 mutations (Phase 3 DESTINY-Lung04)

GU cancers

  • MRG002-ADC (HER2 ADC) for unresectable locally advanced or metastatic bladder cancer (Phase 2 study)
  • RC48-ADC (HER2 ADC) + toripalimab in locally advanced or metastatic bladder cancer.
  • FOR46 (CD46 ADC) in metastatic CRPC (Phase 1a/1b study)

GI cancers

  • Enhertu in HER2-expressing unresectable or recurrent biliary tract cancer (An investigator-initiated phase 2 HERB trial)
  • Enhertu as neoadjuvant treatment for HER2 +  gastric and gastroesophageal junction adenocarcinoma (Phase 2, EPOC2003 trial)

Ovarian cancer

  • STRO-002 (folate receptor alpha ADC) + bevacizumab in advanced epithelial ovarian cancer (phase 1, STRO-002-GM2)

Solid tumors

 SGN-PDL1V (PD-L1 ADC) in advanced solid tumors (phase 1, SGNPDL1V-001)

  • SGN-ALPV (ALPP/ALPPL2 ADC) in advanced solid tumors (phase 1, SGNALPV-001)
  • AZD8205 (B7-H4 ADC) in advanced/metastatic solid tumors (First in human study)
  • ADCT-901(KAAG1 ADC) in select advanced solid tumors  (First-in-human, phase 1 study)
  • OBT076 (CD205 ADC) in advanced/metastatic solid tumors ( a first-in-class phase 1 study)

CBP-1018 and CBP-1008 (bi-ligand-drug conjugate) in advanced solid tumors.(a phase I study)

2. Circulating DNA (ctDNA) adopts the role of a vital & versatile biomarker

Recently FDA released draft guidance for the industry on the use of circulating tumor DNA for early-stage solid tumor drug development. The guidance is intended to help sponsors planning to use ctDNA as a biomarker in cancer clinical trials and/or to support marketing approval of drugs and biological products for treating solid tumor malignancies in the early-stage setting.

Several presentations at ASCO will focus on novel use of ctDNA in patient selection, as a marker for MRD for patient enrichment, as a measure of therapy response, and as an early endpoint in clinical trials.

Key presentations are

 Ct DNA as a non-invasive source for mutation analysis

  • Complementary role for circulating tumor DNA and tumor tissue to detect clinical relevant alterations in patients with CRPC
  • Using cell-free circulating tumor DNA (cfDNA) to identify guideline-relevant biomarkers for therapy selection in 14,000 patients (pts) with metastatic colorectal cancer (mCRC) (Abstract 3601 Poster 395)
  • ESR1 mutations in (ctDNA) are associated with CTCs and increased hormone receptors in metastatic tumor tissues of patients with metastatic breast cancer

CtDNA as a measure of therapy response

ü  Largest evaluation of acquired resistance to sotorasib in KRAS p.G12C-mutated non–small cell lung cancer (NSCLC) and colorectal cancer (CRC): Plasma biomarker analysis of CodeBreaK100. (Abstract 102)
  • Assessing the predictive value of ctDNA on relapse in patients with resected stage IB-IIIA NSCLC treated with adjuvant chemotherapy plus concomitant atezolizumab followed by atezolizumab: BTCRC LUN 19-396.
  • CtDNA shed as a tool to select immune checkpoint inhibitors (ICPI) with or without chemotherapy for patients with advanced NSCLC
  • Dynamic circulating tumor DNA (ctDNA) in monitoring trastuzumab deruxtecan (TDXd) activity for patients (pts) with advanced breast cancer: Preliminary results of a feasibility study.
  • Longitudinal ctDNA whole-exome sequencing (WES) in the phase Ib/II trial of palbociclib and bazedoxifene reveals genomic dynamics and clonal evolution with the acquisition of treatment resistance in hormone receptor-positive, HER2-negative (HR+ HER2-), advanced breast cancer
  • Circulating tumor DNA (ctDNA) and serum thymidine kinase 1 activity (TKa) matched dynamics in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2­–negative (HER2-) advanced breast cancer (ABC) treated in first-line (1L) with ribociclib (RIB) and letrozole (LET) in the BioItaLEE trial.
  • ctDNA in treatment response monitoring in patients with relapsed gynecologic malignancies.
  • Methylated circulating tumor DNA (cfMeDIP) as a predictive biomarker of clinical outcome in pan-cancer patients (pts) treated with pembrolizumab (P).
  • Circulating tumor DNA (ctDNA) analyses of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor (GIST). (Abstract 101)

CT DNA in MRD analysis

  • MRD detection by ctDNA in relation to radiographic disease progression in patients with stage I-III NSCLC treated with definitive radiation therapy.
  • Leveraging personalized ctDNA for detection and monitoring of MRD in high-risk melanoma.
  • ctDNA detection of MRD as a potential biomarker in localized STS
  • NSAB C-14: CORRECT-MRD II—Second colorectal cancer clinical validation study to predict recurrence using a circulating tumor DNA assay to detect minimal residual disease (Abstract TPS3632 Poster 424a)

CT DNA as marker of recurrence

  • Personalized ctDNA analysis in patients with recurrent/metastatic HNSCC
  • Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical NSCLC.
  • ctDNA and late recurrence in high-risk, hormone receptor-positive, HER2-negative breast cancer (CHiRP).
  • Copy number aberration burden on circulating tumor DNA predicts recurrence risk after neoadjuvant chemotherapy in patients with triple-negative breast cancer: Post-hoc analysis of phase III PEARLY trial.

Other presentations on the use of CTDNA biomarker

Circulating Tumor DNA: An Emerging Tool in Gastrointestinal Cancers

  • Real-world utilization of ctDNA in the management of colorectal cancer.
  • Novel use of ctDNA to identify muscle-invasive and non-organ-confined upper tract urothelial carcinoma.(Abstract 4587 Poster 78)
  • Clinical utility of circulating tumor DNA sequencing with a large panel in patients with advanced soft-tissue sarcomas. (Abstract11550 Poster 454)
  • NK cell activity and methylated HOXA9 circulating tumor DNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors. (Abstract 2552 Poster 207)
  • Next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA) in patients (pts) with advanced hepatocellular carcinoma (HCC) (Abstract 4110 Poster 97)

 

3. T Cell and beyond: Success of cell therapies transitioning in solid tumors

70 presentations ranging from updates from late-phase trials to first in human studies in solid and heme malignancies

Key highlights in heme malignancies

Gilead and Kite Oncology to project CAR-T cell therapy developments
New Sub-analysis to be presented  from Kite’s ZUMA-7 CAR T-cell Therapy Study in Patients Aged 65+ and Data by Tumor Burden Characteristics in Second-Line Large B-cell Lymphoma

  • Legend Biotech will showcase Continued Progress in the Treatment of Multiple Myeloma With Updated Data From BCMA CAR-T Studies

Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM. CAR-T cells manufactured on Gracell’s proprietary FasTCAR platform appear younger, less exhausted, and show enhanced proliferation, persistence, bone marrow migration, and tumor cell clearance with next-day manufacturing, FasTCAR is able to significantly improve cell production efficiency

  • NKARTA to report positive preliminary dose-finding data for two lead engineered natural killer cell programs
  • Autologous CD19-directed CAR T cells produced by the novel PrimeCAR manufacture platform exhibit safety, efficacy, and long persistence profiles in relapsed/refractory B-lineage acute leukemia (r/r B-ALL).
  • Decreasing HPK1 expression in CD19 CAR-T cells: A novel strategy to overcome challenges of cell therapy for adult (r/r) B-ALL. (Abstract 7041)
  • CRC-403: A phase 1/2 study of bbT369, a dual-targeting CAR T-cell drug product with a gene edit, in relapsed and/or refractory B-cell non-Hodgkin lymphoma (NHL). (Abstract TPS7580 Poster 231b)
  • Phase 1/2 study of anbalcabtagene autoleucel, novel anti-CD19 CAR-T cell therapy with dual silencing of PD-1 and TIGIT in relapsed or refractory large B-cell lymphoma (Abstract 7522, Poster 176)
  • Autologous CD7-targeted CAR T-cell therapy for refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma. (Abstract 7035)
  • CAR T-cells effective for post-CART relapse: A new treatment paradigm.

Key highlights in solid tumors

  • Safety, tolerability, and preliminary efficacy results in patients with advanced gastric/gastroesophageal junction adenocarcinoma from a phase Ib/II study of CLDN18.2 CAR T-cell therapy (CT041). (Abstract 4017 Poster 5)
  • Phase 2 Quilt 88 trial of DAMP inducers combined with IL15 superagonist, N-803, and anti–PD-L1 NK cell therapy more than doubles historical overall survival in patients with third- to sixth-line advanced pancreatic cancer. (Abstract 4147 Poster 131)
  • Glypican-3-specific CAR-NKT cells overexpressing BATF3 mediate potent antitumor activity against hepatocellular carcinoma.
  • A phase 1 dose-escalation study of GCC19 CART a novel coupled CAR therapy for subjects with metastatic colorectal cancer (Abstract 3582 Poster 376)

A phase 1 first-in-human dose-finding/randomized phase 2 study of IMM60 and pembrolizumab (PEM) in advanced melanoma and non–small cell lung cancer (NSCLC; IMP-MEL) (Abstract 2582 Poster 237)

  • Phase I/II first-in-human CAR T–targeting MUC1 transmembrane cleavage product (MUC1*) in patients with metastatic breast cancer
  • A phase 1, first-in-human (FIH) study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2 overexpressing solid tumors. (Abstract TPS2677 Poster 327b)
  • Phase I clinical safety and efficacy observation of αPD-1-mesoCAR-T cells in the treatment of advanced gynecologic cancer.
  • Phase I clinical trial to assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of NY-ESO-1–specific TCR T-cells (TAEST16001) in HLA-A*02:01 patients with advanced soft tissue sarcoma. (Abstract 11502)
  • Merkel polyoma virus-specific T-cell receptor transgenic T-cell therapy in PD-1 inhibitor refra
    Racial/ethnic disparities in locoregional recurrence in hormone-receptor positive node-negative breast cancerctory Merkel cell carcinoma. (Abstract 9549 Poster 142)
  • DELTA-1: A global, multicenter, phase 2 study of ITIL-168, an unrestricted autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in adult patients with advanced cutaneous melanoma. (Abstract TPS9594 Poster 185b)

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