723O - Cabozantinib plus atezolizumab in advanced and progressive neoplasms of the endocrine system: A multi-cohort basket phase II trial (CABATEN/GETNE-T1914)

Background

Angiogenesis plays a key role in development and progression of endocrine neoplasms and synergism has been observed when combined with immune-checkpoint inhibitors in other tumors. We aimed to demonstrate the activity and safety of cabozantinib (cabo) plus atezolizumab (atezo) in different endocrine neoplasms refractory to standard therapies.

Methods

This is a prospective, multi-center, open-label, phase II study including patients (pts) with advanced and refractory endocrine tumors in 6 independent cohorts (C): (1) well-differentiated neuroendocrine tumors of the lung (LungNET), (2) anaplastic thyroid cancer (ATC), (3) adrenocortical carcinoma (ACC), (4) pheochromocytoma/ paraganglioma (PPGL), (5) well-differentiated gastroenteropancreatic NET (GEPNET), (6) grade 3 extrapulmonary neuroendocrine neoplasms (G3 EP-NEN). All pts received atezo 1200 mg IV Q3W plus cabo 40 mg/day PO until progression or unacceptable toxicity. The primary endpoint was Overall Response Rate (ORR) by RECIST 1.1. With a Simon II stage design, 1 response of 9 pts/C were needed at 1^st stage to continue accrual in 2^nd stage. C1 and C6 did not pass 1^st stage, and C2 and C4 were closed due to slow accrual.

Results

93 pts were enrolled. Cabo and atezo were administered for a median of 5.8 m (95% CI: 3.4-7.5) and 6.3 m (95% CI: 3.5-7.7), respectively. Most frequent grade ≥3 toxicities were fatigue (7.5%), neutropenia (6.5%) and liver enzyme increase (6.5%). 2 pts died due to drug-related ischemic stroke and pancreatitis. Due to AE’s, cabo and atezo treatment was interrupted in 67.7% and 35.5% of pts, and discontinued in 16.1% and 14% of pts, respectively. Cabo was reduced to 20 mg/day in 41.9% of pts. Survival was similar regardless of cabo reduction.

Table: 723O

Conclusions

Cabo plus atezo showed limited activity in progressive / refractory endocrine malignancies, surpassing the futility threshold in ATC. Atezo does not improve the outcomes of cabo as a single agent in NEN.

Clinical trial identification

EudraCT 2019-002279-32; NCT04400474.

Editorial acknowledgement

We acknowledge MFAR Clinical Research staff for their assistance in the development of this abstract.

Legal entity responsible for the study

Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).

Funding

GETNE through industry partners Ipsen and Roche.

Disclosure

R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Bayer, BMS, HMP, Ipsen, Merck, Midatech, MSD, Novartis, Pharma Mar, Pierre Fabre, Servier; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Other, Honoraria received by spouse for advisory board or invited speaker roles: Abbvie, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. C. López: Financial Interests, Personal, Invited Speaker: AAA, Amgen, AstraZeneca, Bayer, Eisai, Ipsen, Lilly, Merk, Novartis, Pfizer, Roche, Servier; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Eisai, Ipsen, Lilly, Merk, Pfizer, Roche, Servier; Financial Interests, Personal and Institutional, Research Grant: Amgen, AstraZeneca; Financial Interests, Personal, Funding: Bayer, Eisai, Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Coordinating PI: Eisai, Ipsen; Financial Interests, Personal, Steering Committee Member: Ipsen; Financial Interests, Personal, Local PI: Ipsen, Roche; Financial Interests, Personal, Research Grant: Servier. C. Hierro: Financial Interests, Personal, Invited Speaker: MSD, Lilly; Financial Interests, Personal, Research Grant, Principal Investigator of Merk sponsored trial: Merk; Non-Financial Interests, Principal Investigator, Clinical Trial: BMS, Zymeworks, ALX Oncology, AstraZeneca; Other, Travel fees: BMS, Amgen, Roche, Merck. M. Llanos: Financial Interests, Personal, Speaker, Consultant, Advisor: Ipsen, Amgen, Servier, AAA, Eisai, Roche, Merck, Lilly, Bristol, Sanofi. E. Grande: Financial Interests, Personal, Invited Speaker: Adacap, AstraZeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, Ipsen, Janssen, Lilly, Merck KGa, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Astellas, Bayer, MSD, Novartis, Sanofi-Genzyme; Financial Interests, Institutional, Advisory Board: Caris Life Sciences, ONCODNA (Biosequence); Non-Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Lexicon, MTEM/Threshold, Nanostring Technologies, Pfizer, Roche; Non-Financial Interests, Institutional, Coordinating PI: Ipsen; Non-Financial Interests, Personal, Other, AD Board member: Enets. All other authors have declared no conflicts of interest.