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

University of Chicago

Residency, Medicine

University of Washington

Fellowship in Hematology-Oncology, Medicine

Duke University School of Medicine

Grants:

CGX1321-101

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

CO40939

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Nektar

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

AbbVie M14-064

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

AbbVie M16-438

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

BACKGROUND: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC. METHODS: All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS). RESULTS: A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1-14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60-84%). Median PFS and OS were 3.9 months (95% CI, 2.3-4.5) and 7.1 months (95% CI: 5.8-10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes. CONCLUSION: The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study. TRIAL REGISTRATION: This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
Authors
Strickler, JH; Rushing, CN; Niedzwiecki, D; McLeod, A; Altomare, I; Uronis, HE; Hsu, SD; Zafar, SY; Morse, MA; Chang, DZ; Wells, JL; Blackwell, KL; Marcom, PK; Arrowood, C; Bolch, E; Haley, S; Rangwala, FA; Hatch, AJ; Nixon, AB; Hurwitz, HI
MLA Citation
Strickler, John H., et al. “A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer..” Bmc Cancer, vol. 19, no. 1, Nov. 2019. Pubmed, doi:10.1186/s12885-019-6234-8.
URI
https://scholars.duke.edu/individual/pub1417915
PMID
31675952
Source
pubmed
Published In
Bmc Cancer
Volume
19
Published Date
Start Page
1032
DOI
10.1186/s12885-019-6234-8

Safety, Efficacy, and Pharmacokinetics of AMG 510, a Novel KRAS(G12C) Inhibitor, in Patients with Non-Small Cell Lung Cancer

Authors
Govindan, R; Fakih, M; Price, T; Falchook, G; Desai, J; Kuo, J; Strickler, J; Krauss, J; Li, B; Denlinger, C; Durm, G; Ngang, J; Henary, H; Ngarmchamnanrith, G; Rasmussen, E; Morrow, PK; Hong, D
MLA Citation
Govindan, R., et al. “Safety, Efficacy, and Pharmacokinetics of AMG 510, a Novel KRAS(G12C) Inhibitor, in Patients with Non-Small Cell Lung Cancer.” Journal of Thoracic Oncology, vol. 14, no. 11, ELSEVIER SCIENCE INC, 2019, pp. S1125–26.
URI
https://scholars.duke.edu/individual/pub1421379
Source
wos
Published In
Journal of Thoracic Oncology
Volume
14
Published Date
Start Page
S1125
End Page
S1126

P2.15-C Phase 1 Trial Evaluating Safety, Efficacy, and PK of AMG 510, a Novel KRASG12C Inhibitor, in Non-Small Cell Lung Cancer

Authors
Govindan, R; Fakih, MG; Price, TJ; Falchook, GS; Desai, J; Kuo, JC; Strickler, JH; Krauss, JC; Li, BT; Denlinger, CS; Durm, G; Ngang, J; Henary, H; Ngarmchamnanrith, G; Rasmussen, E; Morrow, PK; Hong, DS
MLA Citation
Govindan, R., et al. “P2.15-C Phase 1 Trial Evaluating Safety, Efficacy, and PK of AMG 510, a Novel KRASG12C Inhibitor, in Non-Small Cell Lung Cancer.” Journal of Thoracic Oncology, vol. 14, no. 11, Elsevier BV, 2019, pp. S1191–92. Crossref, doi:10.1016/j.jtho.2019.09.181.
URI
https://scholars.duke.edu/individual/pub1421378
Source
crossref
Published In
Journal of Thoracic Oncology
Volume
14
Published Date
Start Page
S1191
End Page
S1192
DOI
10.1016/j.jtho.2019.09.181

Comprehensive landscape of gene amplifications (amps) in tissue and circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC).

<jats:p> 604 </jats:p><jats:p> Background: Amps, as oncogenic and resistance drivers, have therapeutic implications, but unlike mutations, have been sparsely described in mCRC. Functional account is piecemeal due to vague definitions, limited data on co-occurring alterations and use of primary tissue samples nonrepresentative of tumor heterogeneity. Our aim was to define the amp landscape in mCRC using tissue and ctDNA sequencing. Methods: We performed systematic analyses of copy-number variation in 2 cohorts of mCRC patients (pts) [tissue (TC) (N = 1,134) and ctDNA (BC) (N = 3,218)] who had high sensitivity targeted sequencing with MSK-IMPACT (341-468 genes) or Guardant Health (70-73 genes) panel, respectively. For BC, plasma copy number was adjusted (ApCN) to account for variable tumor DNA shedding using max allele frequency and high amp (HAmp) was defined as &gt; 4 copies (similar to predefined tissue cutoff). Results: 166 (15%) and 405 (13%) pts in TC and BC harbored amp in at least one of 18 genes assessed by both panels (Table). Amp prevalence for individual gene was similar in both cohorts ( r = 0.9; P &lt; .01) with RTK amps ( EGFR, ERBB2, MET, FGFR1/2, PDGFRA) seen in 8% pts. Key RTK amps were enriched in RAS/BRAF wild type (RB WT) compared to mutant (RB MUT) (OR 3.5; P &lt; .01) pts in both cohorts, in contrast to low prevalence RTK and non-RTK amps. Median ApCN was higher for RTKs in RB WT vs MUT cases ( ERBB2: 12 vs 5; P = .02). Using validated EGFRab exposure (EGFRi) ctDNA signature, we found that EGFRi pts had higher prevalence of EGFR, MET, BRAF, KRAS, PIK3CA and FGFR1 amps compared to EGFRab naïve pts. Conclusions: While individually uncommon, amps occur across key oncogenic pathways in mCRC and after adjusting for ctDNA shedding, are seen at similar prevalence in tissue and plasma. Amps in RTKs are seen in 10-12% of RB WT tumors, suggesting clinically relevant roles as oncogenic effectors and targets. After EGFRi, a number of amps emerge, including PIK3CA and FGFR1 amps, not previously implicated in acquired resistance. [Table: see text] </jats:p>
Authors
Raghav, KPS; Yaeger, R; Loree, JM; Dasari, A; Morris, VK; Kee, BK; Raymond, VM; Nagy, RJ; Lanman, RB; Strickler, JH; Corcoran, RB; Overman, MJ; Kopetz, S
MLA Citation
Raghav, Kanwal Pratap Singh, et al. “Comprehensive landscape of gene amplifications (amps) in tissue and circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC)..” Journal of Clinical Oncology, vol. 37, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 604–604. Crossref, doi:10.1200/jco.2019.37.4_suppl.604.
URI
https://scholars.duke.edu/individual/pub1416459
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
604
End Page
604
DOI
10.1200/jco.2019.37.4_suppl.604

Addressing the Conundrum of Bleeding and Cancer Detection With Antithrombotic Therapies for Chronic Atherosclerotic Cardiovascular Disease.

Authors
Roe, MT; Strickler, J
MLA Citation
Roe, Matthew T., and John Strickler. “Addressing the Conundrum of Bleeding and Cancer Detection With Antithrombotic Therapies for Chronic Atherosclerotic Cardiovascular Disease..” Circulation, vol. 140, no. 18, Oct. 2019, pp. 1460–62. Pubmed, doi:10.1161/CIRCULATIONAHA.119.042875.
URI
https://scholars.duke.edu/individual/pub1417914
PMID
31657956
Source
pubmed
Published In
Circulation
Volume
140
Published Date
Start Page
1460
End Page
1462
DOI
10.1161/CIRCULATIONAHA.119.042875