First-in-Human Study of a Novel Nonpeptide Drug Conjugate (CRN09682) in Patients With Somatostatin Receptor 2-Expressing Tumors

MD Daneng Li,; Al Hallak, MD, MS Mohammed Najeeb; MD Lowell Anthony,; Toegel, MD Emily Baiyee; MD, PhD Sreenivasa R Chandana,; MD, MS Arvind N Dasari,; MD, PhD Farshid Dayyani,; MD, MBA Michael J Demeure,; MD Jennifer R Eads,; MD, PhD Rocio Garcia-Carbonero,; MD, Thorvardur Halfdanarson,; MD Jason T Henry,; MD, PhD Tatiana Hernandez,; MD Jorge Hernando,; Mary A Maluccio,; MD Ruoyu Miao,; MD, MSc Manuel Pedregal,; MD, Matthew J Reilley,; MD Sheena Sahota,; MD, PhD, PharmD Michael M Song,; Alexander Spira,; MD Rohit Thummalapalli,; PhD Dylan M Glatt,; PhD Dongli Zhou,; MD David C Metz,; MD, MSc, Bin Zhang,; MD, Emily Bergsland,

doi:10.1530/endoabs.116.T14

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Endocrine Abstracts (2025) 116 T14 | DOI: 10.1530/endoabs.116.T14

NANETS2025 18th Annual Multidisciplinary NET Medical Symposium NANETS 2025 Trials In Progress Section (15 abstracts)

First-in-Human Study of a Novel Nonpeptide Drug Conjugate (CRN09682) in Patients With Somatostatin Receptor 2-Expressing Tumors

Daneng Li, MD¹, Mohammed Najeeb Al Hallak, MD, MS², Lowell Anthony, MD³, Emily Baiyee Toegel, MD⁴, Sreenivasa R Chandana, MD, PhD⁵, Arvind N Dasari, MD, MS⁶, Farshid Dayyani, MD, PhD⁷, Michael J Demeure, MD, MBA⁸, Jennifer R Eads, MD⁹, Rocío Garcia-Carbonero, MD, PhD¹⁰, Thorvardur R Halfdanarson, MD¹¹, Jason T Henry, MD¹², Tatiana Hernández, MD, PhD¹³, Jorge Hernando, MD¹⁴, Mary A Maluccio, MD, MPH¹⁵, Ruoyu Miao, MD¹⁶, Manuel Pedregal, MD, MSc¹⁷, Matthew J Reilley, MD¹⁸, Sheena Sahota, MD¹⁹, Michael M Song, MD, PhD, PharmD²⁰, Spira Alexander²¹, Rohit Thummalapalli, MD²², Dylan M Glatt, PhD²³, Dongli Zhou, PhD²³, David C Metz, MD²³, Bin Zhang, MD, MSc²³ & Emily Bergsland, MD²⁴

Author affiliations

¹City of Hope Comprehensive Cancer Center, Duarte, California, USA; ²Karmanos Cancer Institute and Wayne State University, Detroit, Michigan, USA; ³University of Kentucky, Lexington, Kentucky, USA ⁴University of Colorado Cancer Center, Aurora, Colorado, USA; ⁵START Midwest and The Cancer & Hematology Centers, Grand Rapids, Michigan, USA; ⁶The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; ⁷University of California Irvine, Orange, California, USA; ⁸Hoag Family Cancer Institute, Newport Beach, California, USA; ⁹Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; ¹⁰Hospital Universitario 12 de Octubre, Imas 12, UCM, Madrid, Spain; ¹¹Mayo Clinic, Rochester, Minnesota, USA; ¹²Sarah Cannon Research Institute at HealthOne, Denver, Colorado, USA; ¹³START Barcelona, HM Nou Delfos Hospital, Barcelona, Spain; ¹⁴Vall d’Hebron University Hospital, Barcelona, Spain; ¹⁵LSU Health Sciences Center, New Orleans, Louisiana, USA; ¹⁶Emory University, Atlanta, Georgia, USA; ¹⁷Hospital Universitario Fundación Jiménez Díaz START, Madrid, Spain; ¹⁸University of Virginia Health System, Charlottesville, Virginia, USA; ¹⁹NEXT Oncology, Austin, Texas, USA; ²⁰NEXT Oncology, Dallas, Texas, USA; ²¹NEXT Oncology, Fairfax, Virginia, USA; ²²Memorial Sloan Kettering Cancer Center, New York, New York, USA; ²³Crinetics Pharmaceuticals, Inc., San Diego, California, USA; ²⁴University of California San Francisco, San Francisco, California, USA

Background: Somatostatin receptor 2 (SSTR2) is an established target for the treatment of neuroendocrine tumors (NETs) and a possible target for other solid tumors expressing SSTR2, including breast cancer, melanoma, small cell lung cancer, and meningioma. CRN09682 is a novel, nonradioactive, nonpeptide drug-conjugate (NDC) targeting SSTR2-expressing tumors with a monomethyl auristatin E (MMAE) payload. Here, we report the study design and methodolgy for the first-in-human evaluation of CRN09682.

Methods: This phase 1/2, multicenter, open-label, nonrandomized study consists of two phases: dose escalation and dose expansion. In the dose escalation phase, the primary objective is to evaluate the safety and tolerability of CRN09682, while secondary objectives include evaluation of CRN09682 pharmacokinetics, identification of the maximum tolerated dose (MTD), and selection of the expansion phase dose. Eligible patients with progressive metastatic/unresectable SSTR2-expressing tumors (confirmed by SSTR imaging) will be enrolled in the dose escalation phase. CRN09682 will be administered every 3 weeks via intravenous infusion, at a starting dose based on ICH S9 guidelines. Dose escalation will utilize a BOIN design to establish the MTD. The recommended dose for expansion will be based on the totality of data, including available exposure response from the dose escalation phase. The dose expansion phase will enroll cohorts of patients with SSTR2-expressing neoplasms, including: well-differentiated grade 1-3 pancreatic NETs; well-differentiated grade 1-3 extra-pancreatic NETs; poorly differentiated neuroendocrine carcinomas (NECs; including small- and large-cell pulmonary carcinomas, extrapulmonary NECs, and Merkel cell carcinoma); and, if feasible, relapsed or refractory non-neuroendocrine SSTR2-expressing tumors. Patients will continue therapy until disease progression, unacceptable toxicity, or other discontinuation criteria are met. The primary endpoints in the dose expansion phase are safety and tolerability (eg, incidence of adverse events, dose interruptions). Secondary endpoints include assessments of antitumor activity (eg, objective response rate, duration of response, and disease control rate, based on RECIST 1.1 criteria; progression-free survival, overall survival) and pharmacokinetic assessments.

Results: N/A

Conclusions: Results of this study will be used to inform subsequent clinical trials to investigate the efficacy and safety of CRN09682 for patients with metastatic or locally advanced/unresectable neuroendocrine neoplasms or other SSTR2-expressing tumors.

Abstract ID #33397

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NANETS 2025

North American Neuroendocrine Tumour Society

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Authors

Li, MD Daneng

Najeeb Al Hallak, MD, MS Mohammed

Anthony, MD Lowell

Baiyee Toegel, MD Emily

Chandana, MD, PhD Sreenivasa R

Dasari, MD, MS Arvind N

Dayyani, MD, PhD Farshid

Demeure, MD, MBA Michael J

Eads, MD Jennifer R

Garcia-Carbonero, MD, PhD Rocio

Halfdanarson, MD, Thorvardur

Henry, MD Jason T

Hernandez, MD, PhD Tatiana

Hernando, MD Jorge

Maluccio, Mary A

Miao, MD Ruoyu

Pedregal, MD, MSc Manuel

Reilley, MD, Matthew J

Sahota, MD Sheena

Song, MD, PhD, PharmD Michael M

Spira, Alexander

Thummalapalli, MD Rohit

Glatt, PhD Dylan M

Zhou, PhD Dongli

Metz, MD David C

Zhang, MD, MSc, Bin

Bergsland, MD, Emily

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