Preliminary results from a phase 1 study of the antibody-drug conjugate ABBV-221 in patients with solid tumors likely to express EGFR.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2510-2510 ◽  
Author(s):  
Emiliano Calvo ◽  
James M. Cleary ◽  
Victor Moreno ◽  
Maryella Gifford ◽  
Lisa Roberts-Rapp ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Mitigation Strategies ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Egfr Ligand ◽  
Infusion Reactions ◽  
Antibody Drug

2510 Background: ABBV-221 is a 2nd-generation antibody-drug conjugate (ADC) targeting EGFR based on the 1st-generation ADC ABT-414. ABT-414 shows efficacy in glioblastoma (GBM) patients (pts) with EGFR amplification in ongoing studies. ABBV-221 is an affinity matured monoclonal antibody against EGFR linked to the toxin MMAE. ABBV-221 has higher affinity for overexpressed EGFR than ABT-414, potentially allowing it to target a broader range of tumor types. Methods: This is a Phase 1, multicenter study to determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) of ABBV-221. Pts are required to have an EGFR-dependent cancer to be eligible. Starting dose of ABBV-221: 0.3 mg/kg IV infused over 3 hrs for each 21-day cycle, with alternate dosing schedules utilized (2 wks on, 1 wk off or weekly) to mitigate infusion reactions. Results: As of 11 January 2017, 42 pts were treated (13 colon, 5 head & neck (H&N) cancer, 5 non-small cell lung cancer, 5 GBM, 2 breast, 12 other). Ten dose escalation cohorts have been completed with the last cleared dose 4.5 mg/kg per cycle. Tumor tissue samples were evaluated for EGFR protein expression by IHC, EGFR and EGFR ligand mRNA expression by RNAseq, and the results compared to outcome. The most common adverse event (AE) was infusion reaction in 18/42 pts (43%); 3 pts experienced severe infusion reactions. Several mitigation strategies were used to permit continued dose escalation. The other most common AE was fatigue in 17/42 pts (41%). Only 1 pt had keratitis (Grade 4). Sixteen pts (38%) had stable disease (SD), including 4 pts who remained on study longer than 6 months. One H&N pt who has received 2 cycles of ABBV-221 had an unconfirmed partial response and continues to be treated. This pt had high levels of both EGFR and EGFR ligand. Preliminary pharmacokinetics (PK) analysis suggests ABBV-221 exposures are approximately dose-proportional. Conclusions: Safety, PK, pharmacodynamics, and preliminary efficacy data of ABBV-221 warrant further study in this population. Infusion reactions have been manageable and primarily a first dose phenomenon. The duration of SD in pts with refractory solid tumors is encouraging. Clinical trial information: NCT02365662.

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

scholarly journals First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors

2020 ◽  
Vol 38 (16) ◽  
pp. 1824-1835 ◽  
Author(s):  
Raffit Hassan ◽  
George R. Blumenschein ◽  
Kathleen N. Moore ◽  
Alessandro D. Santin ◽  
Hedy L. Kindler ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Human Study ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Phase Ii Studies ◽  
Antibody Drug

PURPOSE This phase I study, which to our knowledge is the first-in-human study of this kind, investigates the safety, tolerability, pharmacokinetics, and clinical activity of anetumab ravtansine, an antibody–drug conjugate of anti-mesothelin antibody linked to maytansinoid DM4, in patients with advanced, metastatic, or recurrent solid tumors known to express the tumor-differentiation antigen mesothelin. PATIENTS AND METHODS This phase I, open-label, multicenter, dose-escalation and dose-expansion study of anetumab ravtansine enrolled 148 adult patients with multiple solid tumor types. Ten dose-escalation cohorts of patients with advanced or metastatic solid tumors (0.15-7.5 mg/kg) received anetumab ravtansine once every 3 weeks, and 6 expansion cohorts of patients with advanced, recurrent ovarian cancer or malignant mesothelioma received anetumab ravtansine at the maximum tolerated dose once every 3 weeks, 1.8 mg/kg once per week, and 2.2 mg/kg once per week. RESULTS Forty-five patients were enrolled across the 10 dose-escalation cohorts. The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg once every 3 weeks or 2.2 mg/kg once per week. Thirty-two patients were enrolled in the 6.5 mg/kg once-every-3-weeks, 35 in the 1.8 mg/kg once-per-week, and 36 in the 2.2 mg/kg once-per-week expansion cohorts. The most common drug-related adverse events were fatigue, nausea, diarrhea, anorexia, vomiting, peripheral sensory neuropathy, and keratitis/keratopathy. There were no drug-related deaths. Anetumab ravtansine pharmacokinetics were dose proportional; the average half-life was 5.5 days. Among 148 patients with mesothelioma or ovarian, pancreatic, non–small-cell lung, and breast cancers, 1 had a complete response, 11 had partial responses, and 66 had stable disease. High levels of tumor mesothelin expression were detected in patients with clinical activity. CONCLUSION Anetumab ravtansine exhibited a manageable safety and favorable pharmacokinetic profile with encouraging preliminary antitumor activity in heavily pretreated patients with mesothelin-expressing solid tumors. The results allowed for the determination of recommended doses, schedules, and patient populations for anetumab ravtansine in phase II studies.

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

scholarly journals First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, in Patients With Advanced Solid Tumors

2018 ◽  
Vol 36 (33) ◽  
pp. 3298-3306 ◽  
Author(s):  
John H. Strickler ◽  
Colin D. Weekes ◽  
John Nemunaitis ◽  
Ramesh K. Ramanathan ◽  
Rebecca S. Heist ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Human Study ◽  
Maximum Tolerated Dose ◽  
Advanced Solid Tumors ◽  
Antibody Drug Conjugate ◽  
Median Response ◽  
Drug Conjugate ◽  
Antibody Drug

Purpose This first-in-human study evaluated telisotuzumab vedotin (Teliso-V), formerly called ABBV-399, an antibody–drug conjugate of the anti–c-Met monoclonal antibody ABT-700 and monomethyl auristatin E. Materials and Methods For dose escalation, three to six patients with advanced solid tumors were enrolled in eight cohorts (0.15 to 3.3 mg/kg). The dose-expansion phase enrolled patients with non–small-cell lung cancer (NSCLC) with c-Met–overexpressing tumors (c-Met positive; immunohistochemistry membrane H-score ≥ 150). Patients received Teliso-V monotherapy intravenously on day 1 once every 3 weeks. Safety, tolerability, pharmacokinetics, and maximum tolerated dose were determined. Results Forty-eight patients were enrolled (median age, 65 years; 35.4% NSCLC; median four prior therapies). One patient each in the 3.0-mg/kg (n = 9) and 3.3-mg/kg (n = 3) cohorts experienced dose-limiting toxicities. Although the maximum tolerated dose was not formally identified, the recommended phase II dose was defined as 2.7 mg/kg on the basis of overall safety and tolerability. The most frequent treatment-emergent adverse events (any grade) were fatigue (42%), nausea (27%), constipation (27%), decreased appetite (23%), vomiting (21%), dyspnea (21%), diarrhea (19%), peripheral edema (19%), and neuropathy (17%). The most frequent Teliso-V–related grade ≥ 3 adverse events were fatigue, anemia, neutropenia, and hypoalbuminemia (4% each). Teliso-V and total antibody pharmacokinetics were approximately dose proportional, with a mean harmonic half-life of 2 to 4 days each. Prospective screening identified 35 (60%) of 58 patients with c-Met–positive NSCLC. Of 16 patients with c-Met–positive NSCLC who were treated with Teliso-V 2.4 to 3.0 mg/kg, three (18.8%; 95% CI, 4.1% to 45.7%) achieved a partial response (median response duration, 4.8 months; median progression-free survival, 5.7 months; 95% CI, 1.2 months to 15.4 months). No other patients experienced a response. Conclusion Teliso-V monotherapy demonstrated favorable safety and tolerability profiles, with encouraging evidence of antitumor activity in patients with c-Met–positive NSCLC.

Phase 1 dose escalation of XMT-1522, a novel HER2-targeting antibody-drug conjugate (ADC), in patients (pts) with HER2-expressing breast, lung and gastric tumors.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 2546-2546 ◽  
Author(s):  
Erika Paige Hamilton ◽  
Minal A. Barve ◽  
Aditya Bardia ◽  
Muralidhar Beeram ◽  
Johanna C. Bendell ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Antibody Drug Conjugate ◽  
Gastric Tumors ◽  
Drug Conjugate ◽  
Antibody Drug
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