Abstract 490P
Background
In the first-in-human study of tusamitamab ravtansine (NCT02187848), an anti-CEACAM5 antibody-drug conjugate, 100 mg/m2 every 2 weeks (Q2W) showed antitumor activity in heavily pretreated patients with nonsquamous non-small cell lung cancer with high CEACAM5 expression. In the dose-escalation phase, 2 of 18 patients with colorectal cancer (CRC) and 1 of 7 with gastric cancer (GC) had confirmed partial responses (PR). Here, we report results from the CRC and GC dose-expansion cohorts.
Methods
Patients were ≥ 18 years with refractory CRC (all comers) or GC. In the GC cohort, inclusion was restricted to those with high CEACAM5 expression (≥ 2+ intensity in ≥ 50% of tumor cells, as assessed by immunohistochemical analysis of tumor tissue). All patients received tusamitamab ravtansine 100 mg/m2 Q2W. The primary efficacy endpoint was overall objective response. Time to progression (TTP) and treatment-emergent adverse events (AEs) were also assessed.
Results
As of November 19, 2020, 46 patients with CRC and 16 with GC were treated. In the CRC cohort, the median age was 62 years (range, 36–77; 32.6% ≥ 65 years) and 84.1% of patients had high CEACAM5 expression. In the GC cohort, the median age was 59 years (range, 35–77; 37.6% ≥ 65 years). Patients in the CRC and GC cohorts had a median of 4 and 3 prior regimens. In the CRC cohort, the best overall response (BOR) was stable disease (SD) in 12 patients (26.1%) and a median TTP of 1.8 months (95% confidence interval [CI], 1.64–1.91). One patient had an unconfirmed PR. In the GC cohort, the BOR was SD in 6 patients (37.5%) and a median TTP of 1.7 months (95% CI, 1.18-2.60). Treatment-related AEs occurred in 34 (73.9%) and 9 (56.3%) patients in the CRC and GC cohorts. Corneal AEs (keratitis and keratopathy) occurred in 13 (28.3%) and 2 (12.5%) patients in the CRC and GC cohorts, leading to treatment modification in 5 (10.9%) patients and 1 (6.3%) patient. Grade ≥ 3 corneal AEs occurred in 2 patients with CRC and none with GC. Corneal toxicity was manageable with dose delay or modification.
Conclusions
Tusamitamab ravtansine was well tolerated in patients with CRC or GC.
Clinical trial identification
NCT02187848.
Editorial acknowledgement
Medical writing support was provided by Zeshan Mahmood, PharmD, and Alexander Simon of inScience Communications (Philadelphia, PA). This work was performed in accordance with current Good Publication Practice guidelines and funded by Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, CHUGAI, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, IPSEN, MERCK. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Ona Therapeutics, Hutchinson MediPharma International, Avvinity, Scandion Oncology, Sotio Biotech, Inspirna Inc; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb International Corporation, Genentech Inc, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, Pfizer, MedImmune, Menarini, Merus N V, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., Hutchinson Medipharma, HalioDX SAS, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. Y. Kang: Financial Interests, Personal, Other, Consulting fees: Amgen, Novartis, BMS. E. Calvo: Financial Interests, Personal, Full or part-time Employment: START, HM Hospitales Group; Financial Interests, Personal, Leadership Role: START; Financial Interests, Personal, Stocks/Shares: START, Oncoart Associated; Financial Interests, Personal, Other, Honoraria: HM Hospitales Group; Financial Interests, Personal, Advisory Role: Nanobiotix, Janssen-Cilag, PsiOxus Therapeutics, Seattle Genetics, Roche/Genentech, Amcure, TargImmune Therapeutics, Servier, Bristol-Myers Squibb, PharmaMar, Alkermes, Amunix, Adcendo, Anaveon, AstraZeneca/MedImmune, BeiGene, Chugai Pharma, MonTa, MedSIR, MSD Oncology, Nouscom, Novartis, OncoDNA, Sanofi, Syneos Health, T-Knife, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: BeiGene, START; Financial Interests, Institutional, Research Grant: Achilles; Financial Interests, Personal, Other, President and Founder: Foundation INTHEOS (Investigational Therapeutics in Oncological Sciences). M. Provencio Pulla: Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Lilly, Roche, Takeda, Janssen; Non-Financial Interests, Leadership Role, President of Spanish Lung cancer Group: President; Non-Financial Interests, Leadership Role, Insutituto Investigación Sanitaria Puerta de Hierro: Director. Y. Bang: Financial Interests, Personal, Advisory Board: MSD, Merck Serano, Daiichi-Sankyo, Astellas, BeiGene, Samyang Biopharm, Alexo Oncol, Hanmi, Daewoong, Amgen; Financial Interests, Personal, Research Grant: Genentech/Roche, MSD, Merck Serano, Daiichi Sankyo, Astellas, BeiGene, Amgen. F. Barlesi: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Financial Interests, Personal, Research Grant: AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, Takeda; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Financial Interests, Personal, Officer, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre , F. Hoffmann-La Roche, Ltd, Sponsored trials (or ISR). P.L. Bedard: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Bicara, BMS, Amgen, Novartis, Genentech/Roche, Sanofi, Merck, Pfizer, Zymeworks, Nektar Therapeutics, Lilly, SeaGen; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Funding: Servier; Non-Financial Interests, Invited Speaker, Executive Board Member: Breast International Group; Non-Financial Interests, Leadership Role, Chair: AACR Project GENIE; Non-Financial Interests, Leadership Role, Past Chair IND CommitteeMember, Breast Site Steering Committee: Canadian Clinical Trials Group; Non-Financial Interests, Advisory Role: SeaGen, Lilly, Amgen, Merck, BMS, Pfizer, Gilead. J.O. Park: Financial Interests, Personal, Advisory Board: Servier, BMS (Celgene), MedPacto, MediRama; Financial Interests, Personal, Research Grant: Servier, BMS (Celgene), MedPacto. J. Kim: Financial Interests, Personal, Full or part-time Employment: IMBdx; Financial Interests, Personal, Other, Honoraria: Merck, CJ Healthcare, Lilly, Boehringer Ingelheim, AstraZeneca, Abion INC; Financial Interests, Personal, Advisory Role: CJ Healthcare, Abion INC; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Sanofi, Lilly, CJ Healthcare, Hanmi, Ono Pharmaceutical, Pfizer, Novotech, Astellas Pharma, Merck, Alphabioparma, Yuhan, MSD, IL-Yang Pharm; Financial Interests, Personal, Expert Testimony: CJ Healthcare. M. Chadjaa: Financial Interests, Personal, Full or part-time Employment: Sanofi. S. Yoruk: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. J. Delord: Financial Interests, Institutional, Advisory Board: BMS, MSD, Pierre Fabre, Roche; Financial Interests, Institutional, Invited Speaker: Merck Serono; Non-Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, BMS, Genentech, MSD, Transgene. All other authors have declared no conflicts of interest.