IBI310 monotherapy or in combination with sintilimab in patients with advanced melanoma: An open-label phase Ia/1b study.

e15111 Background: IBI310 is a humanized IgG1 monoclonal antibody against CTLA-4. The study evaluates the safety and tolerability of IBI310 alone or in combination with sintilimab, a PD-1 inhibitor, in patients (pts) with advanced melanoma. Methods: This phase 1a/1b study contained three parts: Part A, Part B and Part C (NCT03545971). In Part A, pts with advanced melanoma were treated in an accelerated titration design with 0.3 mg/kg IBI310 (Q3W, IV), or a 3+3 escalation design with 1, 2 or 3 mg/kg IBI310 (Q3W, IV), up to 3 cycles. In Part B, pts with advanced melanoma were administrated in a 3+3 escalation design with 1, 2 or 3 mg/kg IBI310 (Q3W, IV) plus sintilimab (200 mg, Q3W, IV) for 4 cycles, followed by sintilimab maintenance therapy (200 mg, Q3W, IV). Part C was dose expansion of the combination therapy. The primary objective was to determine dose-limiting toxicity (DLT) of IBI310 monotherapy and the second was efficacy of the combination therapy. Tumor evaluation was based on RECIST 1.1. Results: As of Nov 12, 2019, 10 pts were enrolled in Part A (median age 55.5), 6 were mucosal melanoma, 3 were acral melanoma and 1 was non-chronic sun damaged (NCSD) melanoma; 17 pts were enrolled in Part B and C (median age 47.0), only 1 (5.9%) was chronic sun damaged (CSD), and 16 (94.1%) were other melanoma types, including 12.5% (2/16) acral, 31.3% (5/16) mucosal and 56.3% (9/16) NCSD melanomas. No DLTs were observed in both Part A and B. In Part A, 9 pts occurred treatment-related adverse events (TRAEs), most commonly pruritus (4 pts), blood thyroid stimulating hormone increased (2 pts), and asthenia (2 pts). No AEs of ≥ grade 3 were reported. Five pts had stable disease (SD). In Part B and C, 13 pts reported TRAEs, only 1 pt occurred grade 3 TRAE (aspartate aminotransferase increased in 3mg dose level), and others reported grade 2, most commonly pruritus (8 pts), rash (7 pts) and alanine aminotransferase increased (6 pts). No AEs leading to death. In evaluable pts in combination with sintilimab, 1 (NCSD melanoma) of 7 pts (3 NCSD, 1 acral, 2 mucosal and 1 CSD melanoma) reached confirmed partial response (PR) in 2 mg group, and 1 (acral melanoma) of 3 pts (1 acral, 1 mucosal and 1 NCSD melanomas) reached confirmed PR in 3 mg group. Five pts had SD. Part C is currently ongoing. Conclusions: IBI310 monotherapy or in combination with sintilimab were well-tolerated without unanticipated AEs in pts with advanced melanoma. The data preliminarily demonstrate an antitumor activity of the combination therapy in previously treated advanced melanoma (acral and NCSD melanomas). Clinical trial information: NCT03545971 .

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Bortezomib With or Without Irinotecan in Relapsed or Refractory Colorectal Cancer: Results From a Randomized Phase II Study

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.0152 ◽

2008 ◽

Vol 26 (14) ◽

pp. 2320-2326 ◽

Cited By ~ 29

Author(s):

Peter S. Kozuch ◽

Caio Max Rocha-Lima ◽

Tomislav Dragovich ◽

Howard Hochster ◽

Bert H. O'Neil ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Phase Ii ◽

Phase Ii Study ◽

Sensory Neuropathy ◽

Primary Objective ◽

Response To Treatment ◽

Open Label ◽

Open Label Phase ◽

Grade 3

PurposeTo evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC).Patients and MethodsPatients were randomly assigned in a 3:4 ratio to bortezomib 1.5 mg/m2(arm A) or bortezomib 1.3 mg/m2plus irinotecan 125 mg/m2(arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability.ResultsA preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade ≥ 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B.ConclusionBortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC.

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Open-label, phase IIIb, multicenter, expanded access study of everolimus in patients with advanced neuroendocrine tumors (NET).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4138 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4138-4138

Author(s):

Oliver Edgar Bechter ◽

Nicole Unger ◽

Ivan Borbath ◽

Sergio Ricci ◽

Tsann-Long Hwang ◽

...

Keyword(s):

Performance Status ◽

Safety Data ◽

Primary Objective ◽

Phase Iii ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

Expanded Access ◽

Open Label Phase ◽

Grade 3

4138 Background: Everolimus (EVE) antitumor efficacy in patients (pts) with advanced NET was demonstrated in 2 double-blind, placebo (P)–controlled, phase III trials (RADIANT-2 and RADIANT-3). Median PFS in pancreatic (pNET) pts was 11.0 months (EVE) vs. 4.6 months (P) (HR 0.35, 95% CI 0.27-0.45, P <0.001) in RADIANT-3. Median EVE exposure in RADIANT-3 was 38 wks. EVE was approved for advanced pNET in the US and Europe in 2011. An expanded access protocol was launched to gather additional safety data and provide access to EVE for pts with advanced NET while awaiting regulatory approval. Methods: Pts aged ≥18 years with biopsy-proven NET; WHO performance status 0-2; and adequate bone, hepatic, and renal function were enrolled. Main exclusion criteria were poorly differentiated NET and cytotoxic therapy within 4 wks of enrollment. EVE (10 mg/d) was administered until disease progression, unacceptable toxicity, discontinuation, death, commercial availability of EVE, or until May 30, 2012. Pts were enrolled from April 21, 2011 to April 20, 2012. Primary objective was grade 3/4 and serious adverse events (AEs). Secondary objectives included investigator-assessed best overall response rate and PFS. Results: The full analysis set included 246 pts (pNET, n=126; non-pNET, n=120); the safety set included 240 pts (pNET, n=123; non-pNET, n=117). Median age was 61 and 66 years; 54% and 49% were male. Main primary tumor sites in non-pNET pts included small intestine (40%) and lung (22%). Median duration of EVE exposure was 12.1 wks and 24 wks in pNET and non-pNET. At data cutoff, there were 21 and 32 PFS events; 105 and 88 pts were censored. Grade 3/4 AEs were reported in 42.3% and 69.2% of pNET and non-pNET; those reported in ≥10% of pts in pNET and non-pNET included hyperglycemia (12.2% and 5.1%), diarrhea (10.6% and 31.6%), stomatitis (9.8% and 11.1%), nausea (8.1% and 10.3%), and anemia (5.7% and 11.1%). Median investigator-assessed PFS was 7.6 (95% CI 5.52-7.62) months and 10.8 (8.77-Not Estimable) months in pNET and non-pNET. Conclusions: EVE was well tolerated in pts with advanced NET. AEs were similar to those previously reported. Protocol-specified early termination of pts limits the interpretation of PFS medians. Clinical trial information: EudraCT Number: 2010-023032-17.

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Efficacy and safety of sintilimab in combination with chemotherapy in previously untreated advanced or metastatic nonsquamous or squamous NSCLC: two cohorts of an open-label, phase 1b study

Cancer Immunology Immunotherapy ◽

10.1007/s00262-020-02738-x ◽

2020 ◽

Author(s):

Haiping Jiang ◽

Yulong Zheng ◽

Jiong Qian ◽

Chenyu Mao ◽

Xin Xu ◽

...

Keyword(s):

Treatment Response ◽

Objective Response ◽

Nonsmall Cell Lung Cancer ◽

Primary Objective ◽

Open Label ◽

Safety And Efficacy ◽

Open Label Phase ◽

Treatment Naïve ◽

Phase 1B ◽

Grade 3

Abstract Combining chemotherapy with immunotherapy improves the therapeutic outcome for first-line (1L) patients with advance nonsmall-cell lung cancer (NSCLC). Two cohorts of a phase 1b study (NCT02937116) aimed to evaluate the safety and efficacy of sintilimab, a PD-1 inhibitor, plus chemotherapy in 1L patients with nonsquamous and squamous NSCLC (nsqNSCLC/sqNSCLC); and to identify potential biomarkers for treatment response. Treatment-naïve patients with nsqNSCLC were enrolled and intravenously given sintilimab (200 mg), pemetrexed (500 mg/m2), and cisplatin (75 mg/m2), every 3 weeks (Q3W) for 4 cycles in cohort D. Treatment-naïve patients with sqNSCLC were enrolled and intravenously given sintilimab (200 mg), gemcitabine (1250 mg/m2), and cisplatin (75 mg/m2), Q3W, for 6 cycles in cohort E. The primary objective was to evaluate the safety and efficacy of the treatment. The additional objective was to explore biomarkers for the treatment efficacy. Twenty-one patients with nsqNSCLC, and 20 patients with sqNSCLC were enrolled in cohort D and cohort E, respectively. By the data cutoff (April 17, 2019), 8 (38.1%) patients in cohort D and 17 (85.0%) patients in cohort E experienced grade 3–4 adverse events. The median follow-up duration was 16.4 months (14.8–23.0) in cohort D and 15.9 months (11.7–17.7) in cohort E. The objective response rate was 68.4% (95% CI 43.4%, 87.4%) in cohort D and 64.7% (95% CI 38.3%, 85.8%) in cohort E. Neither PD-L1 expression nor tumor mutation burden value was significantly associated with an improved treatment response. Sintilimab plus chemotherapy exhibited manageable toxicity and an encouraging antitumor activity in patients with nsqNSCLC and sqNSCLC.

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Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

Pediatric Rheumatology ◽

10.1186/s12969-020-00488-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ekaterina Alexeeva ◽

Gerd Horneff ◽

Tatyana Dvoryakovskaya ◽

Rina Denisova ◽

Irina Nikishina ◽

...

Keyword(s):

Combination Therapy ◽

Controlled Trial ◽

Randomized Study ◽

Primary Objective ◽

Disease State ◽

Inactive Disease ◽

Open Label ◽

Standard Regimen ◽

Double Blind ◽

Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

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281 JAVELIN Medley VEGF: phase 2 study of avelumab + axitinib in patients with previously treated non-small cell lung cancer (NSCLC) or treatment naive, cisplatin-ineligible urothelial cancer (UC)

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0281 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A307-A307

Author(s):

Gabriella Galffy ◽

Iwona Lugowska ◽

Elena Poddubskaya ◽

Byoung Chul Cho ◽

Myung-Ju Ahn ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Maintenance Treatment ◽

Locally Advanced ◽

Small Cell Lung ◽

Open Label ◽

Platinum Based Chemotherapy ◽

Open Label Phase ◽

Treatment Naïve ◽

Previously Treated ◽

Grade 3

BackgroundAvelumab, a human anti–PD-L1 monoclonal antibody, has shown a manageable safety profile and antitumor activity in multiple tumor types, including platinum-resistant metastatic or recurrent NSCLC,1 and is approved for patients with locally advanced or metastatic UC who have progressed after ≥1 previous line of platinum-based chemotherapy2 3 and as maintenance treatment for those who have not progressed with platinum-based chemotherapy.4 JAVELIN Medley VEGF (NCT03472560) evaluated the efficacy and safety of avelumab + axitinib, a potent inhibitor of VEGFR 1, 2, and 3, in patients with advanced or metastatic NSCLC or UC.MethodsEligible patients with NSCLC had received ≥1 prior platinum-containing therapy and ≤2 prior lines of systemic therapy for locally advanced or metastatic disease; patients with UC were treatment naive in the locally advanced or metastatic setting and ineligible for cisplatin-containing chemotherapy. Patients were immune checkpoint inhibitor naïve and received avelumab 800 mg intravenously every 2 weeks + axitinib 5 mg orally twice daily. The primary endpoint was confirmed objective response (OR) per investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS) and safety. PD-L1 expression was assessed in baseline tumor samples (Ventana SP263 assay). Data have not undergone standard quality checks and are subject to change due to COVID-19–related healthcare burden.ResultsA total of 41 patients with NSCLC and 20 with UC received avelumab + axitinib. The confirmed OR rate was 31.7% (95% CI, 18.1–48.1) in the NSCLC cohort and 10% (95% CI, 1.2–31.7) in the UC cohort (all partial responses); 16 patients (39.0%) and 5 (25.0%) had stable disease, respectively. Responses were observed regardless of PD-L1 expression status. Median PFS was 5.5 months (95% CI, 2.5–7.0) in the NSCLC cohort and 2.3 months (95% CI, 1.8–5.6) in the UC cohort. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 24 patients (58.5%) in the NSCLC cohort; the most common was hypertension (n=7 [17.1%]). Grade ≥3 TRAEs occurred in 9 patients (45.0%) in the UC cohort; the most common were amylase increased, asthenia, decreased appetite, and palmar-plantar erythrodysesthesia syndrome (n=2 [10%] each). One patient in each cohort experienced a TRAE that led to death (gastric perforation and urinary bladder hemorrhage).ConclusionsAvelumab + axitinib showed antitumor activity and a manageable safety profile in patients with advanced or metastatic NSCLC or UC consistent with findings from studies of each drug alone and in combination.Trial RegistrationNCT03472560Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesGulley JL, Rajan A, Spigel DR, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 2017;18:599–610.Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 2018;19:51–64.Bavencio(avelumab) injection. [package insert] Darmstadt, Germany: Merck KGaA; 2019.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed August 19, 2020.

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A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors

Investigational New Drugs ◽

10.1007/s10637-020-01055-5 ◽

2021 ◽

Author(s):

Noboru Yamamoto ◽

Toshio Shimizu ◽

Kan Yonemori ◽

Shigehisa Kitano ◽

Shunsuke Kondo ◽

...

Keyword(s):

Liver Function ◽

Solid Tumors ◽

Dose Escalation ◽

Enzyme Inhibitor ◽

Phase 1 ◽

Maximum Tolerated Dose ◽

Primary Objective ◽

Open Label ◽

Phase 1 Study ◽

Open Label Phase

SummaryBackground This open-label, phase 1 study investigated TAS4464, a potent NEDD8-activating enzyme inhibitor, in patients with advanced/metastatic solid tumors (JapicCTI-173,488; registered 13/01/2017). The primary objective was dose-limiting toxicities (DLTs). Maximum-tolerated dose (MTD) was investigated using an accelerated titration design. Methods The starting 10-mg/m2 dose was followed by an initial accelerated stage (weekly dosing; n = 11). Based on liver function test (LFT) results, a 14-day, 20-mg/m2 dose lead-in period was implemented (weekly dosing with lead-in; n = 6). Results Abnormal LFT changes and gastrointestinal effects were the most common treatment-related adverse events (AEs). DLTs with 56-mg/m2 weekly dosing occurred in 1/5 patients; five patients had grade ≥ 2 abnormal LFT changes at 40- and 56-mg/m2 weekly doses. Further dose escalation ceased because of the possibility of severe abnormal LFT changes occurring. DLTs with weekly dosing with lead-in occurred in 1/5 patients at a 56-mg/m2 dose; MTD could not be determined because discontinuation criteria for additional enrollment at that particular dose level were met. As no further enrollment at lower doses occurred, dose escalation assessment was discontinued. Serious treatment-related AEs, AEs leading to treatment discontinuation, and DLTs were all related to abnormal LFT changes, suggesting that TAS4464 administration could affect liver function. This effect was dose-dependent but considered reversible. Complete or partial responses to TAS4464 were not observed; one patient achieved prolonged stable disease. Conclusions MTD could not be determined due to TAS4464 effects on liver function. Further evaluation of the mechanism of NEDD8-activating enzyme inhibitor-induced abnormal liver function is required. Trial registration number JapicCTI-173,488 (registered with Japan Pharmaceutical Information Center). Registration date 13 January 2017

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Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

npj Breast Cancer ◽

10.1038/s41523-021-00244-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Linda T. Vahdat ◽

Peter Schmid ◽

Andres Forero-Torres ◽

Kimberly Blackwell ◽

Melinda L. Telli ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Primary Endpoint ◽

Triple Negative ◽

Progression Free Survival ◽

Antibody Drug Conjugate ◽

Open Label ◽

Common Grade ◽

Open Label Phase ◽

Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

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Clinical activity of fianlimab (REGN3767), a human anti-LAG-3 monoclonal antibody, combined with cemiplimab (anti-PD-1) in patients (pts) with advanced melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9515 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9515-9515

Author(s):

Omid Hamid ◽

Ding Wang ◽

Tae Min Kim ◽

Sang-We Kim ◽

Nehal J. Lakhani ◽

...

Keyword(s):

Combination Therapy ◽

Adrenal Insufficiency ◽

Safety Profile ◽

Phase 1 ◽

Objective Response ◽

Advanced Melanoma ◽

Clinical Activity ◽

Dose Escalation Study ◽

Treatment Naïve ◽

Grade 3

9515 Background: Fianlimab and cemiplimab are two high-affinity, fully human, hinge-stabilized IgG4 monoclonal antibodies. In a Phase 1 dose escalation study, fianlimab combined with cemiplimab showed an acceptable safety profile and some clinical activity in pts with advanced malignancies. Here, we present safety and clinical activity data from two expansion cohorts of pts with advanced melanoma (anti–programmed cell death/ligand-1 [anti–PD-(L)1] naïve or experienced) who were treated with fianlimab + cemiplimab and had an opportunity for first on-treatment tumor assessment (cut-off date: Jan 4, 2021). Methods: Pts with advanced melanoma who had no prior anti–PD-(L)1 treatment (naïve) or prior anti–PD-(L)1 treatment within 3 months of screening (experienced) received fianlimab 1600 mg + cemiplimab 350 mg by IV infusion every 3 weeks. Tumor measurements were performed every 6 weeks for the first 24 weeks and subsequently every 9 weeks per RECIST v1.1. Results: 48 pts with advanced melanoma were treated with the combination therapy: 33 were anti–PD-(L)1 naïve and 15 were anti–PD-(L)1 experienced (median age: 69 years vs 59 years; male: 66.7% vs 46.7%; Caucasian: 87.9% vs 60%). The safety profile (including immune-related adverse events [AEs]) of fianlimab + cemiplimab combination therapy was similar to that of anti–PD-1 monotherapy with one exception. The rate of adrenal insufficiency, 8.3% (4/48) of pts, is similar to the rate previously observed with anti–PD-1 + anti–cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) combination therapy but higher than that observed with anti–PD-1 monotherapy. Grade ≥3 treatment-emergent AEs (TEAEs) occurred in 35.4% (17/48) of patients; Grade ≥3 serious TEAEs occurred in 22.9% (11/48) of patients; 8.3% (4/48) of patients discontinued treatment due to a TEAE. The most common TEAEs were fatigue (n = 15, 31.3%) and rash (n = 11, 22.9%). By investigator assessment, objective response rate (includes unconfirmed complete [CR] and partial responses [PR]) was 63.6% (3 CRs and 18 PRs) for anti–PD-(L)1 naïve pts and 13.3% (1 CR and 1 PR) for anti–PD-(L)1 experienced pts. Median progression-free survival and median duration of response for the anti–PD-(L)1 treatment naïve cohort have not been reached. Prognostic clinical markers and tumor biomarkers such as expression of LAG-3, PD-L1, and major histocompatibility complex II are being evaluated. Recruitment is ongoing. Conclusions: The safety profile of fianlimab + cemiplimab is similar to that observed with cemiplimab monotherapy and other anti–PD-1s, with the exception of higher rate of adrenal insufficiency. Fianlimab + cemiplimab combination has shown clinical activity for pts with advanced melanoma that is similar to anti–PD-1 + CTLA-4 combination therapy, but with lower demonstrated rates of TEAEs. Clinical trial information: NCT03005782.

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Carfilzomib Thalidomide and Dexamethasone Is Safe and Effective in the Treatment of Relapsed/Refractory Multiple Myeloma: An Open Label Phase II Australasian Leukaemia and Lymphoma Group (ALLG) MM 018/ Asian Myeloma Network (AMN) 002 Study

Blood ◽

10.1182/blood-2020-139174 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 39-40

Author(s):

Hang Quach ◽

Simon J Harrison ◽

Je-Jung Lee ◽

Nichloas Murphy ◽

Jae Hoon Lee ◽

...

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Board Of Directors ◽

Phase Ii ◽

Primary Endpoint ◽

Research Funding ◽

Open Label ◽

Advisory Committees ◽

Open Label Phase ◽

Grade 3

Background: The combination of carfilzomib with immunomodulatory drugs (IMiDs) and dexamethasone is active in multiple myeloma (MM). Carfilzomib, thalidomide, and dexamethasone (KTd) has been studied in upfront MM treatment but has not been studied in the setting of relapsed/refractory myeloma (RRMM). The ALLG MM018/ AMN002 is an open-label phase II study of KTd in patients with RRMM. This study was conducted across 16 sites across Australia, New-Zealand, Singapore, South Korea and Taiwan. Method: Patients with RRMM with 1-3 prior lines of treatment were given carfilzomib [K: 20mg/m2 IV cycle 1 days 1 and 2, 56mg/m2 (36mg/m2 for patients age ≥75 years) from cycle 1 day 8 onwards], thalidomide (T: 100mg po nocte) and dexamethasone [dex: 40mg (20mg for patients age ≥75 years) po weekly], in a 28-day cycle. After 12 cycles, T was omitted, and K was given on days 1,2,15,16 and dex days 1,15 every 28-day cycles for a further six cycles. The primary endpoint was PFS. Secondary endpoints were ORR, overall survival, adverse events, and quality of life (QoL). The study had an 80% power to detect a ≥70% PFS at 6.5 months compared to historical ≤50% PFS at 6.5 months expected with Td (Kropff, M. et al. Haematologica 2012), at a significance level of 0.05. Results: This study has completed accrual. Eighty-three patients [median age of 66 years (42-85)] were enrolled with a median follow up of 15.9 (0.9-26) months. ORR rates were 86.4% (≥VGPR 70.2%). Median PFS was 20m (95% CI 15.9-26m). PFS at 6.5 months was 76.2% (95% CI 73.6-84.9%). Median OS has not been reached, and was 75% at 20 months. The most common grade ≥3/4 AEs were peripheral neuropathy (16%), upper respiratory tract infections (12%), dyspnoea (14%), and hypertension (10%). Grade ≥3/4 cardiac AEs occurred in 6%. The median carfilzomib dose that was delivered was 70.7% (32.8-92.6%) of the target dose. Thus far, 41% of patients have completed the intended 18 cycles of treatment. 21% of patients ceased therapy early. The most common reason for early treatment cessation was disease progression (30%) and adverse events (15%). Fifteen patients (18%) have died, 11 were due to MM, two from infection, one from an ischaemic cardiac event, and one from a traffic accident. QoL, as measured by the EQ-5D-5L instrument, remained stable throughout treatment. Conclusion: The ALLG MM018/AMN 002 study has met its primary endpoint. The KTd schedule as outlined in this study is efficacious in patients with RRMM, resulting in a prolonged PFS and a safety profile in line with previous reports for each of carfilzomib and thalidomide. KTd is an active option in jurisdictions where the cost of other IMiDs prohibits regulatory funding. Comparisons of efficacy and adverse events between the Caucasian and Asian populations will be presented at the meeting. Disclosures Quach: Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Sanofi: Consultancy, Research Funding. Harrison:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; CRISPR Therapeutics: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: wrt panobinostat; Haemalogix: Consultancy. Augustson:Roche: Other: Support of parent study and funding of editorial support. Campbell:Amgen, Novartis, Roche, Janssen, Celgene (BMS): Research Funding; AstraZeneca, Janssen, Roche, Amgen, CSL Behring, Novartis: Consultancy. Soo:Hanmi: Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

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Update on overall survival (OS) of RESCUE: An open-label, phase 2 trial of camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (HCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4076 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4076-4076

Author(s):

Yun Zhang ◽

Jianming Xu ◽

Jie Shen ◽

Shanzhi Gu ◽

Lihua Wu ◽

...

Keyword(s):

Combination Therapy ◽

Objective Response ◽

Advanced Hepatocellular Carcinoma ◽

Second Line ◽

First Line ◽

Open Label ◽

Durable Response ◽

Advanced Hcc ◽

Phase 2 Trial ◽

Open Label Phase

4076 Background: C+A combination therapy displayed high objective response rate, disease control rate, and durable response with a manageable safety profile in patients (pts) with advanced HCC. Here we performed an updated analysis of OS to characterize the OS benefit of C+A in HCC pts. Methods: 70 pts in first-line cohort and 120 pts in second-line cohort were enrolled. Median OS and 2-year OS rate were evaluated via updated data (data cutoff, 3 January, 2021). Median time from enrollment to data cutoff of the total population (N = 190) was 29.1 months (range, 24.0-33.7). Results: OS events had occurred in 58.6% pts in first-line cohort and 60.0% pts in second-line cohort. The median OS was 20.1 months (95% CI, 14.9-NR) and 2-year OS rate was 43.3% (95% CI, 31.3-54.7) in first-line cohort. The median OS was 21.8 months (95% CI, 17.3-26.8) and 2-year OS rate was 44.6% (95% CI, 35.5-53.3) in second-line cohort. Conclusions: Long-term follow-up of C+A demonstrated remarkable survival benefit in advanced HCC pts, which further suggested that C+A is a promising combination therapy in advanced HCC pts. Clinical trial information: NCT03463876.

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