John Strickler

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2005

The University of Chicago

Residency, Medicine

University of Washington

Fellowship in Hematology-Oncology, Medicine

Duke University School of Medicine

Grants:

A Phase 1/1b first-in-human dose escalation and expansion study for theevaluation of safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of SAR439459 administered intravenously as monotherapy and in combination with REGN2810 in adult

Administered By
Duke Cancer Institute
Awarded By
Sanofi US
Role
Principal Investigator
Start Date
End Date

A Phase 1 Open-label Dose Escalation and Dose Expansion Study of CGX1321 in Subjects with Advanced Solid Tumors and Phase 1b Study of CGX1321 in Combination with Pembrolizumab in Subjects with Advanced Gastrointestinal Tumors

Administered By
Duke Cancer Institute
Awarded By
Curegenix Inc.
Role
Principal Investigator
Start Date
End Date

A PHASE Ib, MULTICENTER, OPEN-LABELSTUDY TO EVALUATE THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF CIBISATAMAB IN COMBINATION WITH ATEZOLIZUMAB AFTER PRETREATMENT WITH OBINUTUZUMAB IN PATIENTS WITH PREVIOUSLY TREATED METASTATIC, MICROSATELLITE-STABL

Administered By
Duke Cancer Institute
Awarded By
Genentech, Inc.
Role
Principal Investigator
Start Date
End Date

A PHASE 1/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY OF NKTR-262 IN COMBINATION WITH NKTR-214 AND IN COMBINATION WITH NKTR-214 PLUS NIVOLUMAB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMOR MALIGNANCIES

Administered By
Duke Cancer Institute
Awarded By
Nektar Therapeutics
Role
Principal Investigator
Start Date
End Date

Phase 2 Study Comparing Efficacy and Safety of ABT-165 plus FOLFIRI vs Bevacizumab plus FOLFIRI in Metastatic Colorectal Cancer Previously Treated with Fluoropyrimidine/Oxaliplatin and Bevacizumab

Administered By
Duke Cancer Institute
Awarded By
AbbVie Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

Assessment of HER2 (<i>ERBB2</i>) amplification (HER2amp) using blood-based circulating tumor DNA (ctDNA) next generation sequencing (NGS) and correlation with tissue-based testing in metastatic colorectal cancer (mCRC).

<jats:p> 3589 </jats:p><jats:p> Background: HER2 amplified mCRC has emerged as a unique clinical subset, characterized by resistance to anti-EGFR therapy and response to anti-HER2 strategies. Accurate identification and quantification of HER2amp has predictive value for efficacy of anti-HER2 therapies and appropriate patient selection. Despite availability and use of various tumor tissue-based and blood-based assays for detecting HER2amp, data on cross-performance of these platforms are lacking. Methods: Leveraging a multicenter international consortium (Italy, Japan and USA), we generated a large cohort (N = 353) of mCRC patients (pts), tested for HER2amp using both tissue and blood. Tissue testing was done using immunohistochemistry (IHC), in-situ hybridization (ISH) and (NGS). ctDNA NGS was performed using CLIA-certified Guardant360 ctDNA assay, capable of detecting HER2 copy number (CN) variations. The primary endpoint was to correlate HER2 gene CNs in tissue (tCN) and plasma (pCN). Descriptive statistics, spearman correlation (r) and Fisher’s exact test were used. Results: Baseline tumors characteristics included right-sided primary in 234 (23%), proficient mismatch repair in 264 (98%) and RAS/BRAF wild type (WT) genotype in 194 (67%) pts. Tissue testing was done by IHC, ISH and NGS in 76%, 64% and 74% pts, respectively. A total of 177 pts had HER2amp detected by at least one test: 116 (66%), 157 (89%) and 96 (54%) of which had tissue +, ctDNA +, and both tissue and ctDNA + disease, respectively. Discordant cases consisted of 20 (6%) with positivity in tumor only and 61 (17%) in ctDNA only. Sensitivity, specificity, positive and negative predictive values of ctDNA assay (vis-à-vis tissue) were 83%, 74%, 61% and 90% respectively. Among HER2amp pts, median (range) HER2/CEP17 (ISH) ratio, tCN and pCN were 5.2 (2–12), 11.6 (2–700) and 3.5 (2–122), respectively. The pCN showed strong correlation with ISH ratio (r = 0.69) and tCN (r = 0.68) (P &lt; 0.001). Median pCN differed significantly between pts with HER2 IHC 3+ (12.0), 2+ (2.2) and 0/1+ (2.0) tumors (P &lt; 0.001). High HER2amp (pCN &gt; 4.0) appeared to be enriched with tissue + cases (69% vs 8% [OR 24.6, P &lt; 0.001]), tumor tissue HER2 + status (IHC3+ [75%] vs IHC2+ISH+ [50%] vs IHC2+/ISH- or IHC0/1+ [12%], P &lt; 0.001), HER2 tCN &gt; 6 (79% vs 31% [OR 8.7, P &lt; 0.001]) and RAS/BRAF WT tumors (41% vs 17% [OR 3.5, P = 0.064) but not left sidedness (41% vs 38%; OR 1.1; P = 0.82). Conclusions: In this large diverse cohort of mCRC, we demonstrated correlation of HER2 tCN and pCN obtained by tissue-based and blood-based ctDNA assay. Further prospective efforts are needed to standardize this cross-platform quantification of HER2amp to facilitate robust clinical application of HER2 therapies. This effort shows the value of strategic international partnership in furthering research for rare cancer subsets. </jats:p>
Authors
Raghav, KPS; Nakamura, Y; Marsoni, S; Strickler, JH; Yaeger, R; Shah, AT; Okamoto, W; Crisafulli, G; Nagy, R; Raymond, VM; Routbort, M; Siena, S; Corcoran, RB; Bardelli, A; Kopetz, S; Yoshino, T
MLA Citation
Raghav, Kanwal Pratap Singh, et al. “Assessment of HER2 (ERBB2) amplification (HER2amp) using blood-based circulating tumor DNA (ctDNA) next generation sequencing (NGS) and correlation with tissue-based testing in metastatic colorectal cancer (mCRC).Journal of Clinical Oncology, vol. 39, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 3589–3589. Crossref, doi:10.1200/jco.2021.39.15_suppl.3589.
URI
https://scholars.duke.edu/individual/pub1503063
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
3589
End Page
3589
DOI
10.1200/jco.2021.39.15_suppl.3589

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study.

Aim: This phase II study investigated safety and efficacy of dilpacimab or bevacizumab plus FOLFIRI in patients with previously treated metastatic colorectal cancer (mCRC). Materials & methods: Overall, 66 patients were treated (n = 34 dilpacimab + FOLFIRI; n = 32 bevacizumab + FOLFIRI). Progression-free survival, overall survival, response rates and tolerability were assessed. Results: Median progression-free survival for dilpacimab + FOLFIRI compared with bevacizumab + FOLFIRI was 3.78 months (95% CI: 2.07-7.20) versus 7.36 months (95% CI: 5.68-10.55) (hazard ratio: 3.57; 95% CI: 1.57-8.11; stratified). Median overall survival: 7.95 months for dilpacimab + FOLFIRI; not reached for bevacizumab + FOLFIRI. Objective response rates: 5.6% for dilpacimab + FOLFIRI and 14.7% for bevacizumab + FOLFIRI. Patients treated with dilpacimab + FOLFIRI experienced serious treatment-related adverse events (n = 4; 11.8%), including one case of intestinal perforation leading to death; none were reported for bevacizumab + FOLFIRI. Conclusion: Treatment with dilpacimab + FOLFIRI was not well tolerated and did not provide clinical benefit to patients with mCRC compared with bevacizumab + FOLFIRI. Trial Registration Number: NCT03368859 (Clinicaltrials.gov).
Authors
Strickler, JH; Cubillo, A; Liang, J-T; Matrana, M; Kozloff, M; Lowe, T; Blaney, M; Sahtout, M; Naumovski, L; Wainberg, ZA
MLA Citation
Strickler, John H., et al. “Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study.Future Oncol, Aug. 2022. Pubmed, doi:10.2217/fon-2021-1603.
URI
https://scholars.duke.edu/individual/pub1532745
PMID
35920133
Source
pubmed
Published In
Future Oncol
Published Date
DOI
10.2217/fon-2021-1603

Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC).

<jats:p> 9047 </jats:p><jats:p> Background: Upregulation of CD73 in multiple cancers increases adenosine production, leading to local immunosuppression. Oleclumab, a human IgG1λ mAb, inhibits CD73 function and may increase antitumor immunity. Initial data from a Phase I, first-in-human, dose-escalation and expansion study showed that oleclumab ± durvalumab had manageable safety and encouraging clinical activity in pts with advanced CRC or PDAC. We report updated safety and activity in these cohorts and the first results in an expansion cohort of pts with advanced EGFRm NSCLC. Methods: Previously treated pts with histologically or cytologically confirmed microsatellite stable CRC, PDAC, or EGFRm NSCLC received oleclumab 5–40 mg/kg (escalation) and 40 mg/kg (expansion) IV Q2W, alone (escalation only) or with durvalumab 10 mg/kg IV Q2W. The primary objective was safety; secondary efficacy objectives included objective response (OR) per RECIST v1.1 and duration of response (DoR). Results: 66 pts were enrolled in the escalation phase (35 CRC, 31 PDAC) and 126 in the expansion phase (42 CRC, 42 PDAC, 42 EGFRm NSCLC). At data cutoff (DCO; June 9, 2020), the median number of oleclumab doses was 4 in pts on monotherapy (range 1–26) and 4 in pts on combination therapy across both phases (range 1–76). In the escalation phase, there were no DLTs in pts on monotherapy or combination therapy; treatment-related adverse events (TRAEs) occurred in 54.8% of pts on monotherapy (Grade 3–4 in 7.1%) and 54.2% of pts on combination therapy (Grade 3–4 in 20.8%); fatigue was the most common TRAE with both regimens. No TRAEs resulted in death. In previous interim analyses before this DCO, no ORs were reported in the escalation phase. In the expansion phase, 5 pts were treated for ≥12 mos; 6 pts were ongoing at DCO. TRAEs occurred in 54.0% (Grade 3–5 in 15.1%); the most common TRAEs were fatigue (15.1%), diarrhea (9.5%), and rash (7.1%). One pt had a TRAE resulting in death (systemic inflammatory response syndrome). ORs were seen in 1 CRC pt (DoR 35.9+ mos [+ = ongoing response]), 2 PDAC pts (DoR 22.1+ and 28.6+ mos), and 4 EGFRm NSCLC pts (DoR range 5.6 to 15.7+ mos, median not reached; only 1 of the 4 pts had ≥25% programmed cell death ligand-1 [PD-L1]+ tumor cells). Nine CRC pts, 8 PDAC pts, and 9 EGFRm NSCLC pts had SD. Of 6 pts with matched biopsies who received combination therapy, 5 had increases in CD8+ T cells, PD-L1, and granzyme B. Baseline tumor CD73 expression and association with clinical response will be presented. Conclusions: Oleclumab ± durvalumab had a tolerable safety profile and combination therapy showed promising antitumor activity in EGFRm NSCLC. ORs and SD were durable, even in tumor types that are generally immunotherapy-resistant. Clinical trial information: NCT02503774. </jats:p>
Authors
Bendell, JC; LoRusso, P; Overman, MJ; Noonan, AM; Kim, D-W; Strickler, J; Kim, S-W; Clarke, SJ; George, TJ; Grimison, PS; Barve, MA; Amin, MA; Desai, J; Wise-Draper, T; Cooper, Z; Elgeioushi, N; Mueller, NK; Kumar, R; Wu, KY; Patel, SP
MLA Citation
Bendell, Johanna C., et al. “Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC).Journal of Clinical Oncology, vol. 39, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 9047–9047. Crossref, doi:10.1200/jco.2021.39.15_suppl.9047.
URI
https://scholars.duke.edu/individual/pub1503064
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
9047
End Page
9047
DOI
10.1200/jco.2021.39.15_suppl.9047

BRAF-Mutated Advanced Colorectal Cancer: A Rapidly Changing Therapeutic Landscape.

BRAF-mutated advanced colorectal cancer is a relatively small but critical subset of this tumor type on the basis of prognostic and predictive implications. BRAF alterations in colorectal cancer are classified into three functional categories on the basis of signaling mechanisms, with the class I BRAFV600E mutation occurring most frequently in colorectal cancer. Functional categorization of BRAF mutations in colorectal cancer demonstrates distinct mitogen-activated protein kinase pathway signaling. On the basis of recent clinical trials, current standard-of-care therapies for patients with BRAFV600E-mutated metastatic colorectal cancer include first-line cytotoxic chemotherapy plus bevacizumab and subsequent therapy with the BRAF inhibitor encorafenib and antiepidermal growth factor receptor antibody cetuximab. Treatment regimens currently under exploration in BRAFV600E-mutant metastatic colorectal cancer include combinatorial options of various pathway-targeted therapies, cytotoxic chemotherapy, and/or immune checkpoint blockade, among others. Circumvention of adaptive and acquired resistance to BRAF-targeted therapies is a significant challenge to be overcome in BRAF-mutated advanced colorectal cancer.
Authors
Ciombor, KK; Strickler, JH; Bekaii-Saab, TS; Yaeger, R
MLA Citation
Ciombor, Kristen K., et al. “BRAF-Mutated Advanced Colorectal Cancer: A Rapidly Changing Therapeutic Landscape.J Clin Oncol, June 2022, p. JCO2102541. Pubmed, doi:10.1200/JCO.21.02541.
URI
https://scholars.duke.edu/individual/pub1524064
PMID
35649231
Source
pubmed
Published In
Journal of Clinical Oncology
Published Date
Start Page
JCO2102541
DOI
10.1200/JCO.21.02541

393 A phase 1/2 study of SBT6050 combined with trastuzumab deruxtecan (T-DXd) or trastuzumab and tucatinib with or without capecitabine in patients with HER2-expressing or HER2-amplified cancers

<jats:sec><jats:title>Background</jats:title><jats:p>SBT6050 is a novel therapeutic comprising a selective small molecule toll-like receptor 8 (TLR8) agonist linked to the HER2-directed monoclonal antibody pertuzumab, allowing for combination with trastuzumab-based agents and regimens. SBT6050 is designed to activate myeloid cells in tumors expressing moderate to high levels of HER2. TLR8 agonism directly activates myeloid cells, including macrophages and dendritic cells (DCs), and secondarily activates NK and T cells, inducing a broad spectrum of anti-tumor immune mechanisms. SBT6050 is currently being tested as a single agent and in combination with checkpoint inhibitors (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04460456">NCT04460456</jats:ext-link>). Initial results show early evidence of anti-tumor effects, activation of myeloid and NK/T cells, and a safety profile consistent with an immune activator that is generally non-overlapping with that of T-DXd or tucatinib-based regimens.A strong scientific rationale supports the combination of SBT6050 with T-DXd and SBT6050 with trastuzumab and tucatinib ± capecitabine. Both treatment regimens drive tumor cell death and release of tumor neoantigens. SBT6050 can enhance tumor neoantigen presentation and subsequent activation of T cell responses through its direct activation of DCs. SBT6050 combined with T-DXd or trastuzumab and tucatinib ± capecitabine is postulated to drive increased anti-tumor T cell responses. In addition, T-DXd and trastuzumab support antibody-dependent cell mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) and SBT6050 can enhance both functions. SBT6050 activates myeloid cells to secrete cytokines that amplify ADCC by NK cells. Additionally, SBT6050 activation downmodulates SIRPα on the surface of myeloid cells which can increase ADCP through attenuation of the CD47-SIRPα interaction. Consistent with this mechanism of action, in preclinical studies in mice, the combination of trastuzumab and a mouse surrogate of SBT6050 led to enhanced activity in the HER2-positive NCI-N87 human tumor xenograft model compared to either agent alone.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Protocol SBT6050-201 is a phase 1/2, open-label, dose-escalation and expansion study evaluating SBT6050 in combination with either T-DXd (Part 1) or tucatinib and trastuzumab +/- capecitabine (Part 2). Eligible patients are at least 18 years old, have HER2-positive metastatic breast cancer, gastric/GEJ cancer, colorectal cancer, or HER2-expressing or amplified NSCLC, and have received at least one prior therapy for metastatic disease. Patients will receive SBT6050 subcutaneously q3wk starting at a dose with demonstrated pharmacodynamic activity in phase 1. Pharmacodynamic markers of myeloid and NK/T cell activation will be assessed in peripheral blood and on-treatment tumor biopsies. Circulating tumor DNA will be evaluated as an exploratory assessment.</jats:p></jats:sec><jats:sec><jats:title>Ethics Approval</jats:title><jats:p>This clinical study has not yet obtained ethics approval or started enrollment. All participants will be required to give informed consent before taking part.</jats:p></jats:sec>
Authors
Klempner, S; Strickler, J; Gourley, L; Jacquemont, C; Bhatia, V; Hunder, N; Odegard, V; Piha-Paul, S
MLA Citation
Klempner, Samuel, et al. “393 A phase 1/2 study of SBT6050 combined with trastuzumab deruxtecan (T-DXd) or trastuzumab and tucatinib with or without capecitabine in patients with HER2-expressing or HER2-amplified cancers.” Journal for Immunotherapy of Cancer, vol. 9, no. Suppl 2, BMJ, 2021, pp. A426–A426. Crossref, doi:10.1136/jitc-2021-sitc2021.393.
URI
https://scholars.duke.edu/individual/pub1518163
Source
crossref
Published In
Journal for Immunotherapy of Cancer
Volume
9
Published Date
Start Page
A426
End Page
A426
DOI
10.1136/jitc-2021-sitc2021.393