scholarly journals Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: First-in-human dose-escalation study

2022 ◽  
Author(s):  
A. Gazzah ◽  
P.L. Bedard ◽  
C. Hierro ◽  
Y.-K. Kang ◽  
A. Abdul Razak ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Advanced Solid Tumors ◽  
Antibody Drug Conjugate ◽  
Dose Escalation Study ◽  
Drug Conjugate ◽  
Human Dose ◽  
Antibody Drug

scholarly journals Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors

Cancer ◽  
2017 ◽  
Vol 123 (16) ◽  
pp. 3080-3087 ◽  
Author(s):  
Kathleen N. Moore ◽  
Hossein Borghaei ◽  
David M. O'Malley ◽  
Woondong Jeong ◽  
Shelly M. Seward ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Folate Receptor ◽  
Phase 1 ◽  
Antibody Drug Conjugate ◽  
Dose Escalation Study ◽  
Drug Conjugate ◽  
Antibody Drug

First-in-human dose-escalation study of anti-EGFR ADC MRG003 in patients with relapsed/refractory solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3550-3550 ◽  
Author(s):  
Rui-hua Xu ◽  
Miao-Zhen Qiu ◽  
Yang Zhang ◽  
Xiao-Li Wei ◽  
Chaohong Hu
Keyword(s):  
Antitumor Activity ◽  
Adverse Events ◽  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Single Agent ◽  
Antibody Drug Conjugate ◽  
Dose Escalation Study ◽  
Egfr Expression ◽  
Human Dose

3550 Background: MRG003 is a novel antibody drug conjugate (ADC) composed of a fully human anti-EGFR IgG1 monoclonal antibody conjugated to a microtubule disrupting agent monomethyl auristatin E (MMAE). MRG003 is presently being tested in an ongoing phase I study for safety, pharmacokinetics, and preliminary antitumor activity in patients (pts) with solid tumors (CTR20180310). Methods: In the phase I dose escalation study of a traditional (3+3) design, pts with relapsed or refractory cancers received single agent MRG003 once every 3 weeks (Q3W) for a maximum of 8 treatment cycles. The starting dose of MRG003 is 0.1 mg/kg, followed by 0.3, 0.6, 1.0, 1.5, 2.0, 2.5, and 3.0 mg/kg. Observations included adverse events (AEs), dose-limiting toxicity (DLT), and antitumor activity which is assessed every two cycles. Results: A total of twenty-two pts with colorectal (CRC, n = 15), nasopharyngeal (NPC, n = 3), head and neck (H&N, n = 2), esophageal (EC, n = 1), and duodenal (DC, n = 1) cancer were enrolled in the dose escalation. The median age of pts was 56.5 years. The MTD identified was 2.5 mg/kg. Commonly observed adverse events were anemia (50%), AST increase (41%), decreased appetite (41%), rash (36%), pruritus (36%), asthenia (36%), and proteinuria (32%). Majority of AEs were mild to moderate in severity. EGFR expression in patients’ tumor samples was determined retrospectively by a validated IHC method in a central laboratory. Nine out of 22 pts tested were EGFR positive. Among these 9 EGFR positive pts, one with NPC in the 2.5 mg/kg cohort had partial response, four had stable disease (one with H&N in the 1.5 mg/kg, one each with NPC and H&N in the 2.0 mg/kg, and one with EC in the 2.5 mg/kg cohorts). The disease control rate (DCR) at doses ≥1.5 mg/kg was 100% for the EGFR positive pts. Conclusions: The dose escalation study of MRG003 showed manageable safety profiles and encouraging preliminary antitumor activity in pts with EGFR-positive solid tumors. MRG003 is currently being evaluated as a single agent in phase I dose expansion cohorts to further assess safety, PK, and antitumor activity. Clinical trial information: CTR20180310 .

scholarly journals A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors

2018 ◽  
Vol 36 (5) ◽  
pp. 836-847 ◽  
Author(s):  
Gentry T. King ◽  
Keith D. Eaton ◽  
Brandon R. Beagle ◽  
Christopher J. Zopf ◽  
Gilbert Y. Wong ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Antibody Drug Conjugate ◽  
Dose Escalation Study ◽  
Drug Conjugate ◽  
Antibody Drug

Phase 1, open-label, dose-escalation and expansion study of ABBV-399, an antibody drug conjugate (ADC) targeting c-Met, in patients (pts) with advanced solid tumors.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 2510-2510 ◽  
Author(s):  
John H. Strickler ◽  
John J. Nemunaitis ◽  
Colin D. Weekes ◽  
Ramesh K. Ramanathan ◽  
Eric Angevin ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Advanced Solid Tumors ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Drug Conjugate ◽  
Label Dose ◽  
Antibody Drug

A phase I/II, two-part, multicenter, first-in-human study of DS-7300a in patients with advanced solid malignant tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3646-TPS3646
Author(s):  
Johanna C. Bendell ◽  
Toshihiko Doi ◽  
Manish R. Patel ◽  
Sarina Anne Piha-Paul ◽  
Shiraj Sen ◽  
...  
Keyword(s):  
United States ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Topoisomerase I ◽  
Human Study ◽  
Advanced Solid Tumors ◽  
Antibody Drug Conjugate ◽  
Antibody Drug

TPS3646 Background: B7 homologue 3 (B7-H3) is a protein that is overexpressed in various cancer types, including lung, head and neck squamous cell carcinoma, prostate, esophageal, and breast. B7-H3 overexpression is associated with poor prognosis because it promotes increased invasive and metastatic potential of cancer cells (Dong P, et al. Front Oncol. 2018;8:264). Currently, no B7-H3–targeted cancer therapies are approved. DS-7300a is an antibody-drug conjugate composed of a humanized anti–B7-H3 IgG1 monoclonal antibody (MABX-9001a) conjugated to a drug linker that releases its payload upon internalization by cancer cells. The payload, DXd, is an exatecan derivative that inhibits topoisomerase I, an enzyme that relaxes supercoiled DNA for replication and transcription. DS-7300a induced apoptosis in cancer cells in vitro and showed potent antitumor activity in xenograft models of various types of solid tumors in vivo. Methods: This phase 1/2, multicenter, nonrandomized, open-label, first-in-human study of DS-7300a is ongoing in the United States and Japan in patients with selected advanced solid tumors (NCT04145622). This study has 2 parts: dose escalation (part 1) and dose expansion (part 2). Primary objectives are to evaluate the safety, tolerability, and antitumor activity of DS-7300a and to determine the maximum tolerated dose or recommended dose for the expansion part. Secondary objectives include the pharmacokinetic characterization of DS-7300a, determination of the total levels of anti–B7-H3 antibody and the drug component (DXd), and assessment of the incidence of anti-drug antibodies against DS-7300a. Key inclusion criteria are age ≥ 18 years (United States) or ≥ 20 years (Japan), an ECOG performance status of 0 or 1, ≥ 1 measurable lesion according to RECIST 1.1 as assessed by the investigator, and consent to provide pre- and on-treatment tissue samples (mandatory if clinically allowed and not contraindicated). Key exclusion criteria include prior treatment with orlotamab, enoblituzumab, other B7-H3–targeted agents, or an antibody-drug conjugate that is conjugated with a topoisomerase I inhibitor. Dose expansion will start with 3 cohorts, including patients with selected advanced solid tumors. In both parts, DS-7300a will be administered intravenously on day 1 of each 21-day cycle. During dose escalation, the starting dose of DS-7300a is 0.8 mg/kg. This trial is currently in the dose-escalation part. Clinical trial information: NCT04145622 .

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