Clinical activity and safety of simlukafusp alfa, an engineered interleukin-2 variant targeted to fibroblast activation protein-α, combined with atezolizumab in patients with recurrent or metastatic cervical cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5510-5510
Author(s):  
Antoine Italiano ◽  
Loic Verlingue ◽  
Hans Prenen ◽  
Eva M. Guerra ◽  
Diego Tosi ◽  
...  
Keyword(s):  
Objective Response ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cervical Squamous Cell Carcinoma ◽  
Median Number ◽  
Fibroblast Activation Protein ◽  
Clinical Activity ◽  
Fibroblast Activation ◽  
Metastatic Setting

5510 Background: Simlukafusp alfa (SIM; FAP-IL2v) comprises an interleukin-2 variant (IL-2v) moiety and an antibody against fibroblast activation protein-α (FAP). The binding of SIM to FAP, expressed on cancer-associated fibroblasts, accounts for retention and accumulation in malignant lesions. The engineered IL-2v moiety has an abolished binding to IL-2Rα while the affinity to IL-2Rβγ is retained, resulting in activation of immune effector CD8 T and NK cells, but not of regulatory T cells, and therefore may augment activity of PD-(L)1 inhibitors. Methods: The clinical activity and safety of the SIM and atezolizumab (ATZ) combination in patients with recurrent or metastatic (R/M) cervical squamous cell carcinoma (SCC) were evaluated in a phase 2 basket study (NCT03386721). Patients (pts) were treated with SIM 10 mg IV and ATZ 1200 mg IV once every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST v1.1 assessed by investigators. Secondary endpoints were: disease control rate (DCR), duration of response (DoR), progression free survival (PFS). Results: 47 Pts with ECOG ≥1 and median age of 53 years (range: 25-69) were enrolled. All pts were checkpoint inhibitor naïve and 40 (85%) had ≥ 1 previous lines of therapy in the metastatic setting. The median number of cycles was 6 (range: 1-29). The ORR was 27% (90% CI: 18, 39) and DCR was 71% (90% CI: 58, 80) in 44 response-evaluable patients: 2 (5%) had complete response, 10 (23%) partial response, and 19 (43%) stable disease. Responses were observed across PD-L1 subgroups (SP142 assay, IC/TC cut-off ≥ 1%) with 8/22 and 4/18 responders in PD-L1+ and PD-L1- patients, respectively. Responses were durable, the median DoR was 13.3 months (95% CI: 7.6, 14.7). PFS probability at 6 months was 0.4 (95% CI: 0.27, 0.59). The most common adverse events (AE) (reported in > 30% patients), irrespective of relatedness to treatment and severity, were pyrexia (74.5%), anemia (48.9%), asthenia (48.9%), AST increased (44.7%), nausea (42.6%), ALT increased (42.6%), vomiting (36.2%) and diarrhea (31.9%). Grade 3 and 4 AEs related to SIM were observed in 63.8 % and 29.8 % of pts, respectively, while serious AEs (SAE) related to SIM were reported in 40.4%. The most common SAEs (reported in > 5% pts) irrespective of relatedness to treatment were infusion related reaction (14.9%), pyrexia (6.4%) and hydronephrosis (6.4%). One Grade 5 event occurred, which was unrelated to treatment. Conclusions: SIM in combination with ATZ demonstrated an acceptable safety profile in pts with R/M cervical SCC. The anti-tumor activity compares favorably to the approved PD-1 inhibitors in this setting and supports further exploration of IL-2v and checkpoint inhibition in this patient population of high unmet medical need. Clinical trial information: NCT03386721.

Investigate the efficacy of immunotherapy for treatment of pancreatic adenocarcinoma (PDAC) with mismatch repair deficiency (dMMR).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 415-415
Author(s):  
Arish Noor ◽  
Luis E. Aguirre ◽  
Kirsten Blue ◽  
Trenton Avriett ◽  
Estrella M. Carballido ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Cancer Center ◽  
Duration Of Response

415 Background: Immune checkpoint inhibitors (ICI) have been approved in solid tumors with dMMR. However, only limited data are available for PDAC with dMMR given the rarity of dMMR in PDAC. We evaluated efficacy of ICIs in PDAC with dMMR. Methods: Retrospective clinical and pathologic data were collected for patients (pts) with pancreatic adenocarcinoma from May 2017 to June 2020 at Moffitt cancer center. Results: We identified 10 pts with dMMR PDAC. The median age was 64.5 years (range: 42-86) and 4 pts were male. 4 pts had resectable disease, 3 had locally advanced and 3 had metastatic disease at initial diagnosis. MSH6 deficiency (def) was found in 2 cases, PMS2 def in 2, MLH/PMS2 def in 5, and MSH2/MSH6 in 1. 7 pts were treated with ICIs. 3 pts had locally advanced and 4 had metastatic disease when they started ICIs. 5 received Pembrolizumab (pem), 1 received ipilimumab/ nivolumab (ipi/nivo), and 1 received pem then ipi/nivo after progressive disease (PD) on pem. The median number of prior lines of chemotherapy was 1 (range 0-2). 6 pts were evaluable, and 1 had rapid disease progression after 1 dose of pem. Among 6 evaluable pts, 3 had an objective response (1: complete response and 2: partial response), and 2 had stable disease (SD). Median progression-free survival was 8.2 mo, and median overall survival was not reached with median follow-up (FU) of 6.8 mo. The median duration of response was not reached with a median FU of 22.6 mo. The pt with CR remained disease-free for up to 22 months. The pt whose treatment was switched to ipi/nivo after PD on pem achieved SD > 4mo on ipi/nivo. While on immunotherapy, one patient with ipi/nivo developed immunotherapy associated rash requiring systemic steroids, and another on pem developed hypothyroidism requiring levothyroxine. Conclusions: This series suggest ICIs can provide durable clinical efficacy in pts with dMMR PDAC.

scholarly journals Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2985
Author(s):  
Ian Chau ◽  
Nicolas Penel ◽  
Andres O. Soriano ◽  
Hendrik-Tobias Arkenau ◽  
Jennifer Cultrera ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Metastatic Setting ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Combined Positive Score ◽  
Grade 3

Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Tumors were PD-L1-positive (combined positive score ≥ 1) in 19 and -negative in 6 patients. Eighteen patients experienced grade 3 treatment-related adverse events, most commonly hypertension (14%) and elevated alanine/aspartate aminotransferase (11% each), with no grade 4 or 5 reported. The ORR was 25% (PD-L1-positive, 32%; PD-L1-negative, 17%) with duration of response not reached. PFS was 5.6 months (PD-L1-positive, 8.6 months; PD-L1-negative, 4.3 months), and OS 14.6 months (PD-L1-positive, 17.3 months; PD-L1-negative, 11.3 months). Acknowledging study design limitations, ramucirumab plus pembrolizumab had encouraging durable clinical activity with no unexpected toxicities in treatment-naïve biomarker-unselected metastatic G/GEJ cancer, and improved outcomes in patients with PD-L1-positive tumors.

scholarly journals Clinical activity, safety, and PK/PD from a phase I study of RO6874281, a fibroblast activation protein (FAP) targeted interleukin-2 variant (IL-2v)

2018 ◽  
Vol 29 ◽  
pp. viii134-viii135 ◽  
Author(s):  
I. Melero ◽  
E. Castanon Alvarez ◽  
M. Mau-Sorensen ◽  
U.N. Lassen ◽  
M.P. Lolkema ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Interleukin 2 ◽  
Fibroblast Activation Protein ◽  
Clinical Activity ◽  
Fibroblast Activation

Phase II Activity of Belinostat (PXD-101), Carboplatin, and Paclitaxel in Women With Previously Treated Ovarian Cancer

2012 ◽  
Vol 22 (6) ◽  
pp. 979-986 ◽  
Author(s):  
Don S. Dizon ◽  
Lars Damstrup ◽  
Neil J. Finkler ◽  
Ulrik Lassen ◽  
Paul Celano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Clinical Activity ◽  
Phase 2 ◽  
Resistant Disease ◽  
Novel Approach

BackgroundPreclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC).MethodsThirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m2 daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m2 given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design.ResultsThe median age was 60 years (range, 39–80 years), and patients had received a median of 3 prior regimens (range, 1–4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1–23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%–61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drug-related adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0–23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%–66%). Median overall survival was not reached during study follow-up.ConclusionsBelinostat, carboplatin, and paclitaxel combined was reasonably well tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Egbert F. Smit ◽  
Kazuhiko Nakagawa ◽  
Misako Nagasaka ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

Clinical benefit (CB) of high-dose interleukin-2 (HD IL-2) in clear cell (cc) metastatic renal cell carcinoma (mRCC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 461-461
Author(s):  
Neeraj Agarwal ◽  
Kinjal Parikh ◽  
Srinivas Kiran Tantravahi ◽  
Hilda Crispin ◽  
Joan Van Atta ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Clear Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose ◽  
Select Group ◽  
Best Response

461 Background: HD IL-2, an immunotherapy, is a standard of care for a select group of patients (pts) with mRCC. Generally objective response (OR) rates, i.e. complete response (CR) + partial response (PR), of 16-20% are discussed with pts, but not disease stabilization (SD). Recent data suggest that cancer immunotherapy may improve survival without inducing OR. Thus, treatment with HD IL-2 may provide survival benefit to an additional group of pts not experiencing OR, but only SD as the best response. Here we report CB ( OR+SD), and specifically report outcomes of cc mRCC pts experiencing SD as the best response, on treatment with HD IL-2. Methods: All sequential cc mRCC pts treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000-2012 were included. Pts were evaluated for best response, progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS). Two practitioners independently reviewed HD IL-2 response with discrepancies adjudicated by a third reviewer. Results: 85 pts, 79% male, were identified with a median age of 56 (range 32-76) years. Pts belonged to the following MSKCC risk categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. A CR was identified in 9 (11%), PR in 5 (6%), SD in 26 (31%), progressive disease (PD) in 38 (45%), and unknown/not evaluable (NE) in 7 (8%) pts; yielding a clinical benefit in 40 (47%) pts. The median PFS, TNT, and OS in these individual groups of pts are compared in the table. Conclusions: A clinical benefit of HD IL-2 was achieved in nearly half of all clear cell mRCC pts. OS was not significantly different in OR and SD groups. Even though OR favorably determine outcomes, SD is also an important response criterion, and may be discussed during counseling pts for treatment with HD IL-2. [Table: see text]

Phase Ib study to assess the safety, tolerability, and clinical activity of gedatolisib in combination with palbociclib and either letrozole or fulvestrant in women with metastatic or locally advanced/recurrent breast cancer (B2151009; NCT02684032).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1113-TPS1113 ◽  
Author(s):  
Andres Forero-Torres ◽  
Robert Wesolowski ◽  
Aditya Bardia ◽  
Haresh S. Jhangiani ◽  
Peter Kabos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Primary Endpoint ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Mtor Pathway ◽  
Clinical Activity ◽  
Phase Ib ◽  
Metastatic Setting

TPS1113 Background: Hormone receptor positive (HR+) disease is the most common subset of both early and late stage breast cancer (BC). The majority of women with HR+ metastatic BC (MBC) ultimately develop resistance to endocrine therapy, with a median survival of ~2-3 years. A new standard-of-care strategy to treat HR+ metastatic disease involves the combination of hormone therapy and cyclin-dependent kinase (CDK) 4/6 inhibition, which has demonstrated improved progression-free survival (PFS) in both the first- and later-line metastatic setting. More recently, preclinical data with the dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor gedatolisib (PF-05212384) suggest synergy with the combination of hormone therapy, CDK 4/6 inhibition, and inhibition of the PI3K/mTOR pathway. Methods: This phase Ib study includes a dose escalation portion to evaluate dose-limiting toxicities (primary endpoint) and determine the recommended phase II dose for triplet therapy with gedatolisib combined with palbociclib/letrozole or palbociclib/fulvestrant in women with HR+ HER2-negative MBC or locally advanced/recurrent BC, in the first- and later-line setting. Thereafter, a 3-arm expansion for early signals of efficacy will investigate objective response rates (primary endpoint) with gedatolisib combined with palbociclib/letrozole (n = 26), palbociclib/fulvestrant in patients without prior CDK 4/6 inhibition (n = 28), and palbociclib/fulvestrant in patients who have previously received palbociclib (n = 27). The rates of objective response will be compared to historical controls. Secondary endpoints include safety, tumor response, PFS (expansion portion only), pharmacokinetics, and biomarker correlations associated with the PI3K/mTOR pathway. This trial is now recruiting. Clinical trial information: NCT02684032.

A phase II trial of the Wee1 inhibitor adavosertib (AZD1775) in recurrent uterine serous carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6009-6009
Author(s):  
Joyce F. Liu ◽  
Niya Xiong ◽  
Susana M. Campos ◽  
Alexi A. Wright ◽  
Carolyn N. Krasner ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Serous Carcinoma ◽  
Clinical Activity ◽  
Targeted Next Generation Sequencing ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response ◽  
Uterine Serous Carcinoma ◽  
Grade 3

6009 Background: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial carcinoma characterized by TP53 mutations ( > 90%), often concomitantly with oncogenic mutations or amplifications that can increase replication stress. As such, USC may therefore be uniquely sensitive to further interference of cell cycle regulation by Wee1 inhibition. This two-stage single arm Phase 2 study was conducted to assess the activity of the Wee1 inhibitor adavosertib as monotherapy in recurrent USC. Methods: Women with recurrent USC (defined as non-carcinosarcoma uterine cancers with any serous component) were eligible. Patients (pts) were required to have had at least one prior platinum-based chemotherapy regimen; those with known MSI-H/MMRd disease were required to have received prior PD1/PDL1 therapy or to be ineligible for such therapy. There was no upper limit on the number of prior lines pts could have received. All pts were required to have RECIST measurable disease. Pts received adavosertib 300mg daily on days 1 through 5 and 8 through 12 of a 21-day cycle. Coprimary endpoints were objective response and progression-free survival at 6 months (PFS6). Results: Between OCT-11-2018 and SEP-30-2019, 35 pts enrolled on study. Median follow-up is 4.6 months. The median number of prior lines was 3 (range 1-8). 34 pts were considered evaluable for response. In these pts, 9 confirmed and 1 unconfirmed responses were observed, for an ORR of 29.4% (95% CI 15.1-47.5%). The PFS at 6 months was 58.7% (95% CI: 39.5-73.7%). The median PFS is 6.1 months and the median duration of response is 9.0 months. Frequently observed Grade 3 or higher related adverse events included neutropenia (32.3%), anemia (20.6%), and fatigue (23.5%). Immunohistochemistry and targeted next-generation sequencing were performed to investigate potential biomarkers of response. Conclusions: Adavosertib monotherapy demonstrates promising clinical activity in women with USC. The observed monotherapy activity is higher than in other diseases, and additional exploration of the biology of Wee1 inhibition in USC is needed. Further studies of adavosertib in this patient population are planned. Clinical trial information: NCT03668340.

Avelumab in patients with previously treated mesothelioma: Updated phase 1b results from the JAVELIN Solid Tumor trial.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 166-166 ◽  
Author(s):  
Raffit Hassan ◽  
Anish Thomas ◽  
John J. Nemunaitis ◽  
Manish R. Patel ◽  
Jaafar Bennouna ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Best Response ◽  
Duration Of Response ◽  
Previously Treated ◽  
Phase 1B ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

166 Background: Avelumab, a human anti-PD-L1 IgG1 monoclonal antibody, is approved for treatment of metastatic Merkel cell carcinoma (US and EU) and advanced urothelial carcinoma progressed on platinum therapy (US). Here, we report updated phase 1b data for avelumab in patients (pts) with previously treated mesothelioma. Methods: Pts with unresectable pleural or peritoneal mesothelioma whose disease had progressed after platinum and pemetrexed therapy received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs; NCI CTCAE v4.0). Results: As of Dec 31, 2016, 53 pts were treated and followed for a median of 24.8 mos (range 16.8–27.8). Median age was 67 y (range 32–84). Pts had received a median of 2 prior lines of therapy (range 1–8). Confirmed ORR was 9.4% (95% CI 3.1–20.7; complete response in 1.9%, partial response in 7.5%). In pts with 1 (n = 18), 2 (n = 15) or ≥3 (n = 20) prior lines of therapy, ORR was 5.6%, 13.3% and 10.0% respectively. Median duration of response was 15.2 mos (95% CI 11.1–not estimable). 26 pts (49.1%) had stable disease as best response and the disease control rate was 58.5%. Median PFS was 4.1 mos (95% CI 1.4–6.2) and the 6-mo PFS rate was 38.0% (95% CI 24.2–51.7). Median OS was 10.9 mos (95% CI 7.5–21.0) and the 12-mo OS rate was 45.9% (95% CI 31.9–58.8). In evaluable pts with PD-L1+ (n = 16) and PD-L1− (n = 27) tumors (≥5% tumor cell cutoff), ORR was 18.8% (95% CI 4.0–45.6) and 7.4% (95% CI 0.9–24.3), and the 6-mo PFS rate was 37.5% (95% CI 14.1–61.2) and 42.0% (95% CI 23.1–59.8). 43 pts (81.1%) had a treatment-related (TR)AE, most commonly ( > 10%) infusion-related reaction (35.8%; all grade 1/2), chills (15.1%), fatigue (15.1%) and pyrexia (11.3%). 5 pts (9.4%) had a grade ≥3 TRAE. 14 pts (26.4%) had an immune-related AE, which was grade ≥3 in 3 pts (5.7%; pneumonitis, colitis, and type 1 diabetes mellitus). No treatment-related deaths occurred. Conclusions: Avelumab showed clinical activity and acceptable safety in pts with previously treated mesothelioma. Clinical trial information: NCT01772004.

Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 354-354 ◽  
Author(s):  
Scott T. Tagawa ◽  
Bishoy Morris Faltas ◽  
Elaine Tat Lam ◽  
Philip James Saylor ◽  
Aditya Bardia ◽  
...  
Keyword(s):  
Phase I ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Metastatic Urothelial Cancer

354 Background: Patients (pts) with mUC who progress after platinum (PLT)-based chemotherapy and immune checkpoint inhibitor (CPI) therapy have poor outcomes and limited treatment options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate. It consists of a monoclonal antibody targeting Trop-2, an epithelial cell surface antigen overexpressed in UC, conjugated to the active metabolite of irinotecan (SN38). Methods: We performed a phase I/II basket study in pts with advanced solid tumors receiving intravenous SG administered on day 1 and 8 of 21-day cycles, until progression or unacceptable toxicity. CT/MRI scans were obtained at 8-week intervals for response assessment. We evaluated pts with mUC who progressed after ≥1 prior systemic therapy and were treated with SG at the 10 mg/kg dose level. Endpoints included safety, objective response rate (ORR) by RECIST 1.1, clinical benefit rate (CBR; complete response [CR], partial response [PR], or else SD ≥6-mo), and Kaplan-Meier estimated duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: 45 pts (41M/4F; median age 67, range 49-90; ECOG 0/1: 31%/69%) received a median of 2 (range: 1-6) prior treatment lines, including PLT-based chemotherapy (95%) and CPI (38%). 33 had visceral metastases involving liver (n=15), lung (n=27), and other organs (n=5). The ORR was 31% (14/45), with 2 CR and 12 PR. In pts with visceral involvement, the ORR was 27% (9/33). The ORR in CPI-treated pts was 23% (4/17). The median DOR was 12.6 mo (2 pts continuing >2 y), and the CBR was 47% (21/45). Median PFS and OS were 7.3 mo and 18.9 mo, respectively. The AE profile was consistent with prior reports. Grade ≥3 AEs in ≥5% of pts were neutropenia/neutrophil count decreased (38%), anemia (11%), hypophosphatemia (11%), diarrhea (9%), fatigue (9%), and febrile neutropenia (7%). Conclusions: SG demonstrated clinical activity in pts with relapsed/refractory mUC, including CPI-treated pts and pts with visceral disease. A single-arm, open-label, global phase 2 trial is underway to evaluate antitumor activity and safety of SG in advanced UC.(TROPHY-U-01; NCT03547973). Clinical trial information: NCT03547973.

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