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:

REVERCEII (ACCRU-GI-1809): A randomized phase II study of regorafenib followed by anti-EGFR monoclonal antibody therapy versus the reverse sequencing for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin and irino

<jats:p> TPS213 </jats:p><jats:p> Background: Regorafenib (R) is an oral multikinase inhibitor that blocks several protein kinases involved in angiogenesis and oncogenesis; it has a survival benefit in refractory metastatic colorectal cancer (mCRC). The current standard (std) treatment in patients (pts) with RAS wildtype (WT) mCRC is sequential treatment with an anti-EGFR antibody (AEA) followed by R. However, R, which is orally administered once daily, may be more convenient and thus preferable for pts than AEA. REVERCE, a Japanese trial, demonstrated a significant 5.8 month (mo.) survival benefit with regorafenib administered prior to AEA compared to the std sequence. Based off these findings, the proposed phase II trial is to confirm the observed survival benefit from regorafenib sequencing prior to anti-EGFR monoclonal antibody therapy in REVERCE in a US patient population. Methods: REVERCEII is an Academic and Community Cancer Research United (ACCRU) network-led randomized phase II study of R (dose escalation from 80mg to 160mg based on tolerance) prior to AEA (R+AEA) compared to standard sequencing (AEA+R) in pts with refractory RAS WT mCRC. Patients are randomized 1:1 to receive R (Arm A) vs. AEA (with or without irinotecan per investigator choice) (Arm B). At the time of disease progression or intolerance, patients will receive sequential treatment until disease progression. Eligibility criteria include histologically confirmed mCRC, ECOG ≤ 2, acceptable organ function, and patients must have had prior fluoropyrimidine, oxaliplatin and irinotecan, and no prior AEA nor R. The primary objective is to compare the overall survival (OS), the primary endpoint, between evaluable patients (eligible, consented, started protocol treatment) who were randomized to R+AEA (arm A) and AEA+R (arm B). With 83 OS events, we have 87% power to detect an improvement in median OS from 9 months to 14.5 mo., assuming 1-sided significance level of 0.15, and exponential distribution. The total sample size is 124 patients. Secondary endpoints include progression-free survival, objective response, and adverse events. The total study duration is expected to be 3 years. Clinical trial information: NCT04117945. Clinical trial information: 04117945. </jats:p>
Authors
Ahn, DH; Ou, F-S; Sonbol, BB; Wender, D; Klute, K; Jin, Z; Jones, JC; Ulrich, A; Waechter, B; Young, H; Weinberg, BA; Lenz, H-J; Strickler, JH; Bekaii-Saab, TS
MLA Citation
Ahn, Daniel H., et al. “REVERCEII (ACCRU-GI-1809): A randomized phase II study of regorafenib followed by anti-EGFR monoclonal antibody therapy versus the reverse sequencing for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin and irinotecan.Journal of Clinical Oncology, vol. 40, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. TPS213–TPS213. Crossref, doi:10.1200/jco.2022.40.4_suppl.tps213.
URI
https://scholars.duke.edu/individual/pub1518159
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
40
Published Date
Start Page
TPS213
End Page
TPS213
DOI
10.1200/jco.2022.40.4_suppl.tps213

A phase 1b study of sotorasib, a specific and irreversible KRAS<sup>G12C </sup>inhibitor, in combination with other anticancer therapies in advanced colorectal cancer (CRC) and other solid tumors (CodeBreaK 101).

<jats:p> TPS214 </jats:p><jats:p> Background: Approximately 3% of patients (pts) with CRC have the oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation. Sotorasib, a small molecule that specifically and irreversibly inhibits the KRAS G12C mutant protein, has demonstrated modest clinical activity and no dose-limiting toxicities as a single agent in heavily pretreated pts with KRAS p.G12C-mutated CRC. The combination of sotorasib with other anticancer therapies, such as EGFR or MEK inhibitors, may enhance antitumor efficacy and counteract potential escape mechanisms. Other attractive partners for sotorasib in CRC include biologics and chemotherapy combinations. The CodeBreaK 101 master protocol is designed to evaluate safety, tolerability, pharmacokinetics (PK), and efficacy of multiple sotorasib-based combinations in pts with KRAS p.G12C mutated solid tumors. Key subprotocols with CRC combination treatment arms are highlighted here. Methods: This is a phase 1b, open-label study evaluating sotorasib alone and in combination regimens in pts with advanced KRAS p.G12C mutated CRC, NSCLC, and other solid tumors. Key regimens being explored in CRC include (1) Subprotocol A: Sotorasib + trametinib (MEK inhibitor) +/- panitumumab (EGFR inhibitor), (2) Subprotocol H: Sotorasib + panitumumab and sotorasib + panitumumab + FOLFIRI, and (3) Subprotocol M: Sotorasib + bevacizumab-awwb + FOLFIRI or FOLFOX. Key eligibility criteria include advanced or metastatic solid tumor with KRAS p.G12C mutation identified through molecular testing in treatment-naïve and pretreated patients depending on cohort. Primary endpoints include dose-limiting toxicities and treatment-emergent or treatment-related adverse events. Secondary endpoints include PK profile of combination regimens and efficacy (objective response, disease control, duration of response, time to response, and progression-free survival assessed per RECIST 1.1, and overall survival). Enrollment is ongoing. Contact Amgen Medical Information for more information: medinfo@amgen.com (NCT04185883). Abbreviations: EGFR = epidermal growth factor receptor; FOLFIRI = 5-fluorouracil + leucovorin + irinotecan; FOLFOX = 5-fluorouracil + leucovorin + oxaliplatin; MEK = mitogen-activated protein kinase. Clinical trial information: NCT04185883. </jats:p>
Authors
Hong, DS; Yaeger, R; Kuboki, Y; Masuishi, T; Barve, MA; Falchook, GS; Govindan, R; Sohal, D; Kasi, PM; Burns, TF; Langer, CJ; Puri, S; Chan, E; Jafarinasabian, P; Ngarmchamnanrith, G; Rehn, M; Tran, Q; Gandara, DR; Strickler, JH; Fakih, M
MLA Citation
Hong, David S., et al. “A phase 1b study of sotorasib, a specific and irreversible KRASG12C inhibitor, in combination with other anticancer therapies in advanced colorectal cancer (CRC) and other solid tumors (CodeBreaK 101).Journal of Clinical Oncology, vol. 40, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. TPS214–TPS214. Crossref, doi:10.1200/jco.2022.40.4_suppl.tps214.
URI
https://scholars.duke.edu/individual/pub1518160
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
40
Published Date
Start Page
TPS214
End Page
TPS214
DOI
10.1200/jco.2022.40.4_suppl.tps214

Perioperative and oncologic outcomes of hepatic artery infusion pump therapy at an expanding HAI program.

<jats:p> 120 </jats:p><jats:p> Background: Hepatic artery infusion (HAI) is a liver directed therapy to treat unresectable or resected colorectal liver metastases (CRLM) and unresectable intrahepatic cholangiocarcinoma (ICC). Historically, HAI has only been performed at few specialized centers; however, there is increasing expansion to new centers. We previously reported safety outcomes of our index year of HAI therapy. We now report safety, feasibility, efficacy and oncologic outcomes for an expanded cohort of 62 patients in an established HAI program. Methods: Patients selected for HAI by multidisciplinary review were evaluated for demographics and perioperative outcomes. Objective hepatic response was calculated according to RECIST 1.1. Overall, hepatic and extrahepatic progression-free survival (PFS) were calculated by the Kaplan-Meier method on an intent-to-treat basis. Results: 62 patients were treated with HAI from November 2018-September 2021: 46 for unresectable CRLM, 8 as adjuvant HAI for resected CRLM, and 8 for unresectable ICC. Median age was 54.5 years (range 32-80), 58% were male, and 97% received prior chemotherapy (median 12 cycles, range 0-66). Hepatectomy (18, 29%) and/or colectomy/proctectomy (27, 43.5%) was performed concurrently with pump placement, and 19 (30.6%) were performed robotically. Median operating time was 265 minutes (range 130-526), estimated blood loss was 100 mL (range 22-1000) and length of stay was 5 days (range 1-19). HAI-specific complications occurred in 14% (Table). Floxuridine (FUDR) was initiated in 95% of patients a median of 18.5 days after surgery. Of the 38 patients who received HAI for unresectable CRLM and had measurable disease on imaging, 3- and 6-month hepatic disease control was achieved in 86% (8 partial response [PR], 22 stable disease [SD], 5 progressed [PD]) and 89% (1 complete response, 8 PR, 8 SD, 2 PD), respectively. For patients with at least 3 months follow-up, median PFS, hepatic PFS and extrahepatic PFS were 13 months, 13 months, and 13 months, respectively. Conclusions: HAI can be safely and effectively delivered to well-selected patients with CRLM and ICC. Response rates, disease control and PFS in heavily treated patients with unresectable CRLM comparable to high-volume centers can be achieved at new programs with appropriate expertise. These data support the mission of the newly formed HAI Consortium to critically evaluate efficacy and innovation in HAI therapy through multi-institutional collaboration and contemporary prospective trials.[Table: see text] </jats:p>
Authors
Sharib, J; Liu, A; Creasy, J; Wildman-Tobriner, B; Uronis, HE; Strickler, JH; Hsu, DS; Zani, S; Allen, PJ; Lidsky, M
MLA Citation
Sharib, Jeremy, et al. “Perioperative and oncologic outcomes of hepatic artery infusion pump therapy at an expanding HAI program.Journal of Clinical Oncology, vol. 40, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. 120–120. Crossref, doi:10.1200/jco.2022.40.4_suppl.120.
URI
https://scholars.duke.edu/individual/pub1518161
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
40
Published Date
Start Page
120
End Page
120
DOI
10.1200/jco.2022.40.4_suppl.120

MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in progress.

<jats:p> TPS371 </jats:p><jats:p> Background: Tucatinib (TUC), a highly selective HER2-directed tyrosine kinase inhibitor (TKI) approved in multiple regions for HER2+ metastatic breast cancer, is being developed as a novel therapy for patients (pts) with GI tumors including gastric or gastroesophageal junction adenocarcinoma (GEC). While trastuzumab (Tras) with chemotherapy is standard in the 1st-line setting for metastatic HER2+ GEC, no anti-HER2 therapy has demonstrated an OS benefit over chemotherapy as 2nd-line therapy, possibly due to loss of HER2 expression following Tras-based therapy. In GEC xenograft models, dual targeting of HER2 with TUC and Tras showed superior activity to either agent alone.(Kulukian 2020) Interim results from the MOUNTAINEER study have shown promising activity for TUC and Tras for HER2+ mCRC.(Strickler 2019) The MOUNTAINEER-02 study is evaluating the efficacy and safety of TUC with Tras, ramucirumab (Ram), and paclitaxel (Pac) in pts with HER2+ GEC in the 2nd-line setting. Methods: MOUNTAINEER-02 (NCT04499924) is a phase 2/3 study evaluating TUC + Tras with Ram and Pac. Pts receive TUC 300 mg or placebo PO BID, Tras (6 then 4 mg/kg) or placebo (IV on Days 1 and 15 of each 28-day cycle), Pac (IV on Days 1, 8, 15), and Ram (IV on Days 1 and 15). Eligible pts have locally-advanced unresectable or metastatic HER2+ GEC and have received a HER2-directed antibody and 1 prior line of therapy for advanced disease. Pts must be ≥18 years of age, with an ECOG ≤1, and have had no prior exposure to Ram, anti-HER2 or anti-EGFR TKI, HER2-directed antibody-drug conjugates, or taxanes ≤12 months before enrollment. Due to the potential impact of TUC on Pac metabolism, the study will include an initial Pac dose optimization stage. The open-label phase 2 part will determine the recommended dose of Pac (60 or 80 mg/m²) combined with TUC, Tras, and Ram in 6-18 pts, and evaluate safety and activity of the regimen in Cohorts 2A and 2B (30 pts each). The randomized, double-blind, phase 3 part will compare the efficacy and safety of TUC and Tras (Arm 3A; ̃235 pts) vs. placebo (Arm 3B; ̃235 pts), both in combination with Ram and Pac, and also evaluate activity of TUC with Ram and Pac (Arm 3C; ̃30 pts). The dual primary phase 3 endpoints are OS and PFS per investigator, with confirmed ORR as a key secondary endpoint. HER2 status is determined at baseline using a blood-based NGS assay, and IHC/ISH of fresh or archival tumor biopsies, if available. Pts must be HER2+ by blood-based NGS in Cohort 2A and phase 3; in Cohort 2B, pts must be HER2+ in a biopsy taken post-progression during/after 1<jats:sup>st</jats:sup>-line therapy, but HER2-negative by blood-based NGS. Disease assessments per RECISTv1.1 will occur q6 weeks for 36 weeks, then q9 weeks. The pharmacokinetics of TUC, Pac, and their metabolites will be evaluated in a subset of pts, including a cohort with gastrectomies. Enrollment in phase 2 is ongoing. Clinical trial information: NCT04499924. </jats:p>
Authors
Catenacci, DVT; Strickler, JH; Nakamura, Y; Shitara, K; Janjigian, YY; Barzi, A; Bekaii-Saab, TS; Lenz, H-J; Chung, HCC; Tabernero, J; Yoshino, T; Siena, S; Mayor, JG; Palanca-Wessels, MC; Xie, D; Marshall, J
MLA Citation
Catenacci, Daniel V. T., et al. “MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in progress.Journal of Clinical Oncology, vol. 40, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. TPS371–TPS371. Crossref, doi:10.1200/jco.2022.40.4_suppl.tps371.
URI
https://scholars.duke.edu/individual/pub1518162
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
40
Published Date
Start Page
TPS371
End Page
TPS371
DOI
10.1200/jco.2022.40.4_suppl.tps371

Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.

BACKGROUND: Sotorasib, a specific, irreversible KRASG12C protein inhibitor, has shown monotherapy clinical activity in KRASG12C-mutated solid tumours, including colorectal cancer, in the CodeBreaK100 phase 1 trial. We aimed to investigate the activity and safety of sotorasib in phase 2 of the trial. METHODS: In this single-arm, phase 2 trial, adult patients with KRASG12C-mutated advanced solid tumours were enrolled, from 59 medical centres in 11 countries, if they were aged 18 years or older, had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, and had an Eastern Cooperative Oncology Group performance status of 1 or lower. Only data for patients with colorectal cancer, enrolled at 33 medical centres in nine countries, are presented from this basket trial. To be enrolled, the patients had to have progressed after receiving fluoropyrimidine, oxaliplatin, and irinotecan treatment. These patients were administered 960 mg sotorasib orally once per day until disease progression, development of unacceptable side-effects, withdrawal of consent, or death. The primary endpoint was objective response (complete or partial response) as assessed by blinded independent central review. Response was evaluated in patients who received at least one dose of sotorasib and had at least one measurable lesion at baseline; safety was evaluated in patients who received at least one dose of sotorasib. This analysis is a prespecified analysis triggered by the phase 2 colorectal cancer cohort. This study is registered with ClinicalTrials.gov, NCT03600883, and is active but no longer recruiting. FINDINGS: On March 1, 2021, at data cutoff, 62 patients with KRASG12C-mutant colorectal cancer had been enrolled between Aug 14, 2019, and May 21, 2020, and had received at least one dose of sotorasib monotherapy. Objective response was observed in six (9·7%, 95% CI 3·6-19·9) of 62 patients, all with partial response. Treatment-related adverse events at grade 3 occurred in six (10%) patients, the most common of which was diarrhoea (two [3%] of 62 patients), and at grade 4 occurred in one (2%) patient (blood creatine phosphokinase increase); no fatal events were recorded. Serious treatment-related adverse events occurred in two (3%) patients (back pain and acute kidney injury). INTERPRETATION: Although the 9·7% overall response rate did not reach the benchmark, oral administration of sotorasib once per day showed modest anti-tumour activity and manageable safety in these heavily pretreated chemorefractory patients. Sotorasib is under evaluation in combination with other therapeutics to increase potential activity and overcome potential resistance mechanisms. FUNDING: Amgen.
Authors
Fakih, MG; Kopetz, S; Kuboki, Y; Kim, TW; Munster, PN; Krauss, JC; Falchook, GS; Han, S-W; Heinemann, V; Muro, K; Strickler, JH; Hong, DS; Denlinger, CS; Girotto, G; Lee, M-A; Henary, H; Tran, Q; Park, JK; Ngarmchamnanrith, G; Prenen, H; Price, TJ
MLA Citation
Fakih, Marwan G., et al. “Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.Lancet Oncol, vol. 23, no. 1, Jan. 2022, pp. 115–24. Pubmed, doi:10.1016/S1470-2045(21)00605-7.
URI
https://scholars.duke.edu/individual/pub1504259
PMID
34919824
Source
pubmed
Published In
Lancet Oncol
Volume
23
Published Date
Start Page
115
End Page
124
DOI
10.1016/S1470-2045(21)00605-7