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:

A case report of microsatellite instability (MSI)-high, HER2 amplified pancreatic adenocarcinoma with central nervous system metastasis.

Pancreatic adenocarcinoma commonly presents as metastatic disease and harbors a dire prognosis due to its aggressive behavior, propensity for resistance to therapies, and lack of targetable driver mutations. Additionally, despite advances in other cancers, immunotherapy has been ineffective in this disease thus far and treatment remains centered around cytotoxic chemotherapy. Here, we present a case of a patient with pancreatic adenocarcinoma harboring both high microsatellite instability (MSI-H) and HER2 amplification. After an initial response to standard-of-care chemotherapy with FOLFIRINOX followed by progression, she was treated with dual immune checkpoint blockade, which resulted in a period of disease control. This was complicated by the development of autoimmune hypophysitis and an incidental finding of brain metastasis on magnetic resonance imaging (MRI). Her extracranial disease progressed while receiving stereotactic radiosurgery, with findings of lymphangitic spread in her lungs, and her treatment was changed to gemcitabine/nab-paclitaxel with trastuzumab. This resulted in a degree of extracranial disease control, though she experienced progressive brain metastases despite radiation and therapeutic switch to lapatinib and trastuzumab. Ultimately, the patient developed leptomeningeal disease which was not controlled by intrathecal trastuzumab. Given the rarity of central nervous system metastasis, HER2 amplification, and MSI in pancreatic cancer, this patient's presentation represents a confluence of multiple unique features. This case highlights the clinical value of up-front next-generation sequencing in metastatic pancreatic cancer and the ability of pancreatic cancer with actionable molecular variants to develop atypical sites of disease and adaptive resistance.
MLA Citation
DeVito, Nicholas C., et al. “A case report of microsatellite instability (MSI)-high, HER2 amplified pancreatic adenocarcinoma with central nervous system metastasis.Ame Case Rep, vol. 5, 2021, p. 14. Pubmed, doi:10.21037/acr-20-154.
URI
https://scholars.duke.edu/individual/pub1481212
PMID
33912803
Source
pubmed
Published In
Ame Case Rep
Volume
5
Published Date
Start Page
14
DOI
10.21037/acr-20-154

Predictive Value of Combining Biomarkers for Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC. METHODS: We retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB. Optimal cutoff for prediction of response by TMB was determined by receiver operating characteristic analysis, and area under the curve (AUC) was calculated for all 3 biomarkers and combinations. Cox model was used to assess prognostic factors of overall survival (OS) and time to progression (TTP). Survival cutoffs calculated with Kaplan-Meier survival curves were TMB ≥10 mut/Mb, PD-L1 ≥50%, NLR <5, and combined biomarkers. RESULTS: Data from 88 patients treated were analyzed. The optimal TMB cutoff was 9.24 mut/Mb (AUC, 0.62), improving to 0.74 combining all 3 biomarkers. Adjusted Cox model showed that TMB ≥10 mut/Mb was an independent factor of OS (hazard ratio [HR], 0.31; 95% confidence interval; 0.14-0.69; P = .004) and TTP (HR, 0.46; 95% CI, 0.27-0.77; P = .003). The combination of high TMB with positive PD-L1 and low NLR was significantly associated with OS (P = .038) but not TTP. CONCLUSIONS: TMB has modest predictive and prognostic power for clinical outcomes after ICI treatment. The combination of TMB, PD-L1, and NLR status improves this power.
Authors
Kao, C; Powers, E; Wu, Y; Datto, MB; Green, MF; Strickler, JH; Ready, NE; Zhang, T; Clarke, JM
MLA Citation
URI
https://scholars.duke.edu/individual/pub1481799
PMID
33972172
Source
pubmed
Published In
Clin Lung Cancer
Published Date
DOI
10.1016/j.cllc.2021.03.017

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

<jats:p> 228 </jats:p><jats:p> Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m<jats:sup>2</jats:sup> every three weeks and oral C 850mg/m<jats:sup>2</jats:sup> twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After &gt; 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937. </jats:p>
Authors
Uronis, HE; Rushing, C; Blobe, GC; Hsu, SD; Mettu, NB; Wells, JL; Niedzwiecki, D; Hartman, L; Moyer, A; Hurwitz, HI; Strickler, JH
MLA Citation
Uronis, Hope Elizabeth, et al. “KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 228–228. Crossref, doi:10.1200/jco.2021.39.3_suppl.228.
URI
https://scholars.duke.edu/individual/pub1478769
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
228
End Page
228
DOI
10.1200/jco.2021.39.3_suppl.228

PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).

<jats:p> TPS143 </jats:p><jats:p> Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. Blood-based profiling of cell free DNA (cfDNA) can identify genomic alterations that drive acquired EGFR Ab resistance. After discontinuation of anti-EGFR Abs, acquired genomic alterations decay over time to undetectable levels. Some studies have suggested clinical benefit from EGFR Ab rechallenge, but there is limited evidence that EGFR Ab rechallenge improves survival compared to standard of care (SOC) therapies. We hypothesize that cfDNA profiling will identify patients appropriate for panitumumab rechallenge, and that these molecularly selected patients will have improved survival compared to current SOC therapies. Methods: This is a randomized phase II, open label study designed to compare the overall survival (OS) of panitumumab rechallenge versus SOC (investigator choice TAS-102 or regorafenib). Secondary objectives include comparisons of progression free survival, objective response rate, clinical benefit rate, and quality of life as measured by the linear analogue self-assessment (LASA) questionnaire. Eligible patients have radiographically measurable KRAS, NRAS, and BRAF codon 600 wild-type mCRC based on tumor tissue testing, and must have experienced progression or intolerance to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF Ab, and an anti-PD-1 Ab if the tumor has mismatch repair deficiency or is MSI-H. Progression after at least 4 months treatment with an anti-EGFR Ab is required. All patients must be enrolled in the COLOMATE cfDNA screening protocol (NCT03765736) and meet molecular eligibility based on Guardant360 cfDNA profiling (absence of amplification of ERBB2, KRAS, NRAS, and MET; absence of mutations of BRAF, EGFR, ERBB2, KRAS, NRAS, and MET [mutant allele frequency &gt; 0.5%]). Greater than 90 days must have elapsed between the most recent treatment with an anti-EGFR Ab and cfDNA profiling. Dosing for all study drugs is according to clinical SOC. 120 patients will be randomized 1:1 to panitumumab rechallenge or SOC. With 83 OS events, this study will have 80% power to detect an improvement in median OS from 6.5 to 10 months (HR=0.65; 1-sided α= 0.15). This study began enrollment in 6/2020. Recruitment is ongoing at 16 sites in the Academic and Community Cancer Research United (ACCRU) network (ACCRU-GI-1623). Clinical trial information: NCT03992456. </jats:p>
Authors
Strickler, JH; Ou, F-S; Bekaii-Saab, TS; Parseghian, CM; Cercek, A; Ng, K; Sanchez, FA; Bruggeman, S; Larson, JJ; Finley, GG; Hubbard, JM; Wu, C; Lenz, H-J; Kopetz, S; Corcoran, RB
MLA Citation
Strickler, John H., et al. “PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. TPS143–TPS143. Crossref, doi:10.1200/jco.2021.39.3_suppl.tps143.
URI
https://scholars.duke.edu/individual/pub1478790
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
TPS143
End Page
TPS143
DOI
10.1200/jco.2021.39.3_suppl.tps143

MOUNTAINEER:open-label, phase II study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress).

<jats:p> TPS153 </jats:p><jats:p> Background: The clinical benefit of approved therapies in patients (pts) with metastatic colorectal cancer (mCRC) who progress on first- and second-line chemotherapy (FOLFOX and FOLFIRI) is limited. In pts with chemotherapy-refractory RAS wild type mCRC, antibodies targeting EGFR offer a monotherapy response rate of approximately 20% and a progression-free survival (PFS) of 4 months (Price 2014). HER2 is a validated target in gastric and breast cancers, with HER2 amplification occurring in ~3–5% of pts with mCRC. Tucatinib (TUC), recently approved for HER2+ metastatic breast cancer, is a tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR. In pt-derived xenograft models of HER2+ mCRC, the combination of TUC + trastuzumab (TRAS) showed significantly greater antitumor activity compared with either agent alone (Kulukian 2020). The MOUNTAINEER trial was initiated to evaluate the efficacy and safety of TUC in combination with TRAS in pts with HER2+ RAS wild-type mCRC. Interim analysis of the initial 26 pts enrolled in MOUNTAINEER demonstrated an objective response rate (ORR) of 52.2% (12 partial responses [PRs] in 23 evaluable pts), median duration of response of 10.4 months, with a median PFS of 8.1 months and a median overall survival (OS) of 18.7 months (Strickler 2019). Based on these results, the trial was expanded to enable better estimation of ORR and safety. Methods: MOUNTAINEER (NCT03043313) is an open-label, pivotal phase 2 trial that initially consisted of a single cohort of up to 45 pts (Cohort A) treated with TUC (300 mg BID) and TRAS (8 mg/kg IV followed by 6 mg/kg IV every 3 weeks). The trial was expanded to include an additional 70 pts randomized 4:3 into 2 cohorts: Cohort B (N = 40) who will receive TUC + TRAS, and Cohort C (N = 30) who will receive TUC monotherapy. Pts in Cohort C will be treated with TUC (300 mg orally twice daily) with the option to crossover to TUC + TRAS if an objective response is not achieved by 12 weeks, or if progressive disease develops at any time. Eligible pts have RAS wild-type and HER2+ mCRC, and must have previously received regimens that include fluoropyrimidines, oxaliplatin, irinotecan, anti-VEGF therapy, and an anti-PD-1 if the tumor has dMMR proteins or is MSI-H. Pts who have received prior HER2-directed therapies are not eligible. Additionally, pts must have measurable disease and ECOG PS of 0 to 2. The primary endpoint of this trial is confirmed ORR (per RECIST v1.1) in Cohorts A + B as assessed by blinded independent central review. Secondary endpoints include duration of response, PFS, OS, and safety and tolerability. Enrollment is ongoing in the US and planned for the EU. Clinical trial information: NCT03043313. </jats:p>
Authors
Strickler, JH; Ng, K; Cercek, A; Fountzilas, C; Sanchez, FA; Hubbard, JM; Wu, C; Siena, S; Tabernero, J; Van Cutsem, E; Kardosh, A; Saeed, A; Andre, T; Stecher, M; Palanca-Wessels, MC; Bekaii-Saab, TS
MLA Citation
Strickler, John H., et al. “MOUNTAINEER:open-label, phase II study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress).Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. TPS153–TPS153. Crossref, doi:10.1200/jco.2021.39.3_suppl.tps153.
URI
https://scholars.duke.edu/individual/pub1478791
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
TPS153
End Page
TPS153
DOI
10.1200/jco.2021.39.3_suppl.tps153