Background

In the phase III CASPIAN trial, durvalumab (D) in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved the primary endpoint of OS vs EP alone in pts with extensive-stage small-cell lung cancer (ES-SCLC). Here we describe clinically relevant analyses for D + EP vs EP based on PD-L1 expression, progression patterns and PROs.

Methods

Tx-naive ES-SCLC (WHO PS 0/1) pts received 4 cycles of EP plus D q3w followed by maintenance D q4w or up to 6 cycles of EP q3w + prophylactic cranial irradiation (PCI; investigator’s discretion). PD-L1 expression in optional archival tissue was tested by VENTANA PD-L1 (SP263) immunohistochemistry assay. PROs were assessed using EORTC QLQ-C30/LC13 with changes from baseline analysed by time to deterioration (TTD) per Cox proportional hazards.

Results

As of 11 March 2019, 265 and 266 pts had received D + EP and EP, respectively. Of 277 with evaluable samples (D + EP, 151; EP, 126), PD-L1 expression was low (5% and 22% of pts with expression ≥1% in tumour (TC) and immune cells (IC), respectively). Evaluating PD-L1 expression as a continuous variable in either TC or IC indicated no significant impact of PD-L1 on Tx effect between arms for OS (P = 0.54 and 0.23, respectively); nor for PFS and ORR. Progression patterns were similar, although fewer pts developed new lesions at first progression with D + EP vs EP (41.4% vs 47.2%), including lung lesions (8.6% vs 15.2%). The incidence of new brain/CNS metastases was similar between arms (11.6% vs 11.5%), despite PCI allowance in the control arm only. Baseline PRO scores were comparable across all symptoms and functional domains. TTD was longer across all PROs for D + EP (favourable HRs, many with upper 95% CIs <1; Table 1).Table: LBA89

Time to deterioration (TTD) in PROs for D + EP vs. EP*

Conclusions

D + EP provided significant OS benefit over EP alone, while preserving QoL and increasing the time to worsening of symptoms and functioning. PD-L1 expression was low and did not appear to be a predictive biomarker for D + EP.

Clinical trial identification

NCT03043872 (release date: February 6, 2017).

Editorial acknowledgement

Medical writing support was provided by Andrew Gannon, MA, MS, of Cirrus Communications (New York, NY), an Ashfield company, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca PLC.

Disclosure

L. Paz-Ares: Leadership role: Genomica; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Roche; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Pfizer; Honoraria (self), Spouse / Financial dependant: Novartis; Spouse / Financial dependant: Ipsen; Spouse / Financial dependant: SERVIER; Spouse / Financial dependant: Sanofi; Honoraria (self), Spouse / Financial dependant: Amgen; Honoraria (self), Spouse / Financial dependant: Merck; Honoraria (self): Boehringer Ingelheim; Honoraria (self): PharmaMar; Honoraria (self): Celgene; Honoraria (self): Sysmex; Honoraria (self): Incyte. J.W. Goldman: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AbbVie. M.C. Garassino: Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): AstraZeneca; Honoraria (self): Roche. K. Hotta: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self): Ono; Honoraria (self): Nipponkayaku; Honoraria (self): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai. N. Reinmuth: Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Böhrigner Ingelheim; Non-remunerated activity/ies: AbbVie; Honoraria (self), Non-remunerated activity/ies: Hoffmann-La Roche; Honoraria (self): MSD SHARP & DOHME GMBH; Honoraria (self): Takeda; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: Pfizer. Y. Shrestha: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Patel: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H. Mann: Full / Part-time employment: AstraZeneca. H. Jiang: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Özgüroğlu: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas; Travel / Accommodation / Expenses: BMS. Y. Chen: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Genetech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Brystol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Speaker Bureau / Expert testimony: Eli-Lilly ; Honoraria (self), Speaker Bureau / Expert testimony: Guardant Health; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Array Biopharma; Research grant / Funding (institution): ISPEN; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

Background

IMpower133 (NCT02763579), a global phase I/III, double-blind, randomized, placebo-controlled trial, showed that adding atezo (anti–PD-L1) to 1L carboplatin + etoposide for ES-SCLC led to a statistically and clinically significant improvement in OS and progression-free survival (PFS) vs carboplatin + etoposide alone. This combination was US FDA–approved in March 2019. Here we present an exploratory updated OS analysis of IMpower133.

Methods

Patients (pts) without prior systemic tx for ES-SCLC were enrolled. PD-L1 testing was not required for enrolment eligibility, but tissue was collected when possible. Pts were randomised 1:1 to receive four 21-day cycles of carboplatin (AUC 5 mg•mL/min IV, Day 1) + etoposide (100 mg/m² IV, Days 1-3) with either atezo (1200 mg IV, Day 1) or placebo (PBO), then maintenance therapy with atezo or PBO until intolerable toxicity or progression. Pts meeting predefined criteria could receive tx beyond progression. Coprimary endpoints were OS and investigator-assessed PFS. OS interim and final analyses were planned for ≈ 240 and ≈ 306 OS events, respectively. Since OS was statistically significant at the interim analysis, an exploratory updated OS analysis was conducted, and exploratory biomarker analyses are in progress.

Results

201 pts were randomized to the atezo group and 202 to the PBO group. At this updated analysis, 302 OS events had been observed. Median follow-up was 22.9 mo. Median OS remained 12.3 mo in the atezo group and 10.3 mo in the PBO group (HR, 0.76 [95% CI: 0.60, 0.95]; descriptive P = 0.0154). 13% more pts were alive in the atezo group than the PBO group at 12 and 18 mo (Table). Other efficacy analyses, including by PD-L1 status, will be presented.Table: 1736O

Conclusions

The addition of atezo to carboplatin and etoposide continued to provide improvement in OS for 1L ES-SCLC. These results further support this regimen as the new standard of care for untreated ES-SCLC.

Clinical trial identification

NCT02763579.001-Time employment: The Chinese University of Hong Kong; Advisory / Consultancy, Non-remunerated activity/ies: geneDecode Ltd. A. Scherpereel: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD. N. Reinmuth: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Hoffmann La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda. M.C. Garassino: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Otsuka Pharma, BMS, Takeda, Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Dephaforum Srl; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Inivata; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca, Roche; Honoraria (self), Speaker Bureau / Expert testimony: ACCMED; Honoraria (self), Speaker Bureau / Expert testimony: Forum Service Srl; Honoraria (self), Speaker Bureau / Expert testimony: Medscape; Honoraria (self), Speaker Bureau / Expert testimony: McCann Healthcare; Honoraria (self), Speaker Bureau / Expert testimony: SOS Srl; Honoraria (self), Speaker Bureau / Expert testimony: Crems Srl; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Tiziana Sciences, Clovis, Merck, Bayer, GSK; Officer / Board of Directors: Women for Oncology Italy, AIOT; Non-remunerated activity/ies, Scientific Committee/General Member: AIOM, ASCO, AIOT, IASCL, IPOP, TUTOR. J. De Castro Carpeno: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp and Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Takeda; Travel / Accommodation / Expenses: Pierre Favre. R. Califano: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AZ; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly Oncology; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche ; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Research grant / Funding (institution): AbbVie; Leadership role, Non-remunerated activity/ies: ESMO; Research grant / Funding (institution): Clovis; Shareholder / Stockholder / Stock options: The Christie Private Care; Non-remunerated activity/ies: EORTC. M. Nishio: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Merck Serono. F. Orlandi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: F. Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca/MedImmune; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Amgen, Boehringer Ingelheim, Astellas Medivation, Celltrion, . J.A. Alatorre Alexander: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck-Sharp & Domme; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: F. Hoffmann La Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment: Head of Oncology National Institute of Respiratory Diseases Mexico. T.A. Leal: Advisory / Consultancy: Genentech; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Bayer; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Mirati Therapeutics. S. Lam: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. M. McCleland: Full / Part-time employment: Genentech, Inc. Y. Deng: Full / Part-time employment: Genentech, Inc. S. Phan: Full / Part-time employment: Genentech, Inc. L. Horn: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Xcovery; Advisory / Consultancy: Merck; Research grant / Funding (institution): Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Kshipra Desai, PhD, CMPP, of Health Interactions, and funded by F. Hoffmann-La Roche.

Background

The optimal TRT regimen for LSCLC remains to be defined. CALGB 30610/RTOG 0538 started as a 3 arm study designed to discontinue one of 2 experimental TRT arms based on interim toxicity assessment, while the remaining arm would be compared against standard 4500 cGy (twice-daily) TRT.

Methods

Per protocol, the interim endpoint was calculated based on treatment related grade 3+ non-hematologic toxicity, grade 4 hematologic toxicity, failure to complete 4 cycles of chemotherapy, and any grade 5 toxicity. The analysis included the initial 70 patients assigned to each of the 7000 cGy (once daily) and the 6120 cGy (concomitant boost) study arms. The initial analysis was conducted May 21, 2012 and an updated analysis of the same patient population was performed April 15, 2019.

Results

There was not a significant difference in toxicity scoring between the regimens, either in the 2012 assessment or the updated analysis. Overall grade 3, 4, and 5 treatment related adverse events were 21.4%, 54.3%, and 0% for 7000 cGy TRT compared with 20.0%, 57.1% and 1.4% for 6120 cGy TRT, while rates of non-hematologic toxicity were 10.0%. 12.9% and 0% for 7000 cGy TRT compared with 12.9%, 14.3%, and 1.4% with 6120 cGy TRT. Grade 3 pneumonitis was reported in 2 patients (2.9 %) in each cohort. Grade 4 dyspnea was observed in 4 patients (5.7 %) in the 6120 cGy cohort but was not reported in patients treated with 7000 cGy.

Conclusions

Both TRT regimens, 7000 cGy daily and 6120 cGy concomitant boost, concurrent with cisplatin and etoposide chemotherapy, appear to be tolerable without unexpected toxicity. A decision to discontinue the 6120 cGy arm in December 2012 was based on the toxicity distribution, as a significant difference in overall toxicity was not observed. Further details of toxicity and the scoring system applied will be presented. The phase III portion of the study comparing 7000 cGy TRT to 4500 cGy TRT is near completion.

Clinical trial identification

CALGB 30610 / RTOG 0538 Identifier: NCT00632853.

Legal entity responsible for the study

Alliance for Clinical Trials in Oncology.

Funding

National Cancer Institute. Support: U10CA180821, U10CA180882, U10CA180868, U10CA180820, U10CA233330, U10CA180888; https://acknowledgments.alliancefound.org.

Disclosure

All authors have declared no conflicts of interest.

Background

As a multicentre, randomized, double-blind phase II trial, ALTER 1202 (NCT03059797) suggests that anlotinib is a promising treatment option for patients with relapsed SCLC who failed ≥ 2 lines of chemotherapy. The median progress-free survival (PFS) was significantly longer in the anlotinib group compared with the placebo group (4.1 months vs 0.7 months; HR 0.19, 95% CI 0.12 to 0.32], P < 0.0001) as per the 30 June 2018, data cutoff date. Here we report updated OS results in the ITT population while OS events occurred in about 78% patients.

Methods

Eligible either limited- or extensive-stage SCLC patients with disease progression after ≥ 2 lines of chemotherapy were randomized 2:1 to anlotinib or placebo (12 mg PO QD from day 1 to 14, every 3 weeks). The primary endpoint was PFS. OS was a pre-specified secondary endpoint.

Results

Between March 2017 and May 2018, 120 patients from 11 centers were randomized to either anlotinib arm (n = 82) or placebo arm (n = 38). In the final analysis (04 APR 2019), median OS was significantly prolonged about 2.4 months in anlotinib arm (7.3 months vs 4.9 months). OS at this date showed 60 events in anlotinib arm and 33 events in placebo arm (HR 0.53, 95%CI 0.3-0.8; p = 0.0029). Six-month, 1-y survival rates were 63.9%, 30.6% in the anlotinib group and 32.7%, 13.1% in the placebo group. The hazard ratio for OS favored anlotinib in most subgroups, especially for patients with brain metastases (OS 6.3m vs 2.6m; HR 0.23, 95%CI 0.09-0.59; p = 0.0009) and patients that received study drug as third-line therapy (OS 7.3m vs 4.9m; HR 0.50, 95%CI 0.31-0.82; p = 0.0051). No newly adverse events were observed.

Conclusions

The updated results showed that anlotinib prolonged not only PFS but also OS significantly than placebo with favorable safety profile. These data suggested that anlotinib is a promising treatment option for patients with relapsed SCLC who have experienced treatment failure with two lines of chemotherapy.

Clinical trial identification

NCT03059797.

Legal entity responsible for the study

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

Background

ROVA-T is an antibody-drug conjugate targeting delta-like protein 3 (DLL3) that is highly expressed in 80% of SCLC. The reported study (NCT02819999) evaluated ROVA-T alone or in combination with platinum-based chemotherapy (CE) in frontline treatment of ES-SCLC.

Methods

Pts with ES-SCLC (≥18 yr; ECOG PS: 0–1) received 1 cycle of CE prior to enrollment (prior treated CNS lesions allowed; tissue banked for later DLL3 analysis). Four cohorts (Co) were enrolled: single-agent ROVA-T (Co1); ROVA-T induction followed by CE (Co2); ROVA-T + CE (Co3); ROVA-T maintenance after CE (Co4). Co1, 2, and 4 were closed early. Co3 received a total 2 IV doses of ROVA-T (0.1 or 0.2 mg/kg) on day 1 of each 6-wk cycle in combination with 4 doses of CE. Primary objectives of Co3: determine the recommended phase II dose (RP2D), evaluate safety and preliminary efficacy; toxicity was graded per NCI CTCAE v4.3, efficacy assessed via RECIST 1.1.

Results

As of March 2019, 26 pts were dosed: Co1 (4), Co2 (5), Co3 (14), Co4 (3). Median age: 66 yr (46% <65, 54% ≥65); 73% ECOG 1; 27% had baseline brain metastases. Fifteen (60%) pts received 2 doses of ROVA-T; 67% completed 4 doses CE. One pt (16.6%) in Co3 (0.2 mg/kg) experienced DLT: grade 3 bullous dermatitis. Most common drug-related AEs (ROVA-T or CE) were fatigue (57.7%), anemia (38.5%), and neutropenia (34.6%). Most common drug-related AEs by Co: Co1, nausea, dyspnea, and hypoalbuminemia (50% each); Co2, edema peripheral (60%); Co3 (0.1 mg), neutropenia and fatigue (62.5% each); Co3 (0.2 mg), fatigue (83.3%); Co4, fatigue, neutropenia, and anemia (100% each). See table for efficacy data. Biomarker DLL3 response data are pending.Table: 1739O

Conclusions

The safety profile of ROVA-T 0.3 mg/kg monotherapy was challenging, while the tolerability of lower doses of ROVA-T in combination with CE was acceptable. The RP2D for ROVA-T + CE was 0.2 mg/kg. There was no clear evidence benefit of addition of ROVA-T to CE.

Clinical trial identification

NCT02819999.

Editorial acknowledgement

Mary L. Smith, PhD, CMPP, from Aptitude Health, Atlanta, GA, funded by AbbVie.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Disclosure

C. Hann: Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Ascentage; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Genentech/Roche; Research grant / Funding (institution): Merrimack Pharmaceuticals. T. Burns: Advisory / Consultancy: AbbVie Stemcentrx. A. Dowlati: Advisory / Consultancy: Seattle genetics; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: AbbVie; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Roche; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Mirati; Research grant / Funding (institution): BMS. D. Morgensztern: Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Heat Biologics; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: BMS; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Research grant / Funding (institution): Merck; Research grant / Funding (institution): NewLink Genetics; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Stemcentrx; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Baxter; Research grant / Funding (institution): Incyte. M. Koch: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. Y. Chang: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. P. Komarnitsky: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. C. Ludwig: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. H. Nimeiri: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. All other authors have declared no conflicts of interest.