A phase I study of JS001, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with advanced solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3067-3067 ◽  
Author(s):  
Zhihong Chi ◽  
Bixia Tang ◽  
Xinan Sheng ◽  
Lu Si ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Open Label ◽  
Tumor Biopsy ◽  
Elimination Half ◽  
Grade 3 ◽  
Approved Drugs ◽  
Favorable Safety

3067 Background: JS001 blocks the interaction between PD-1 and its ligands and eradicates established tumor in human PD-1 Knock-in mouse model. Methods: A Phase I open-label study is designed to evaluate the safety and tolerability of JS001 in advanced solid tumor pts who are refractory to standard therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg followed by a dose expansion. (Clinical Trial ID: NCT02836795). Results: As of January 27, 2017, pts enrollment has been completed with 36 pts from 3 indications (22 Melanoma; 9 Urothelial Carcinoma; 5 Renal Cell Carcinoma). The majority of melanomas are acral and mucosal origin. No DLT was observed and no MTD was reached in the study. The most common treatment-related AEs were grade 1/2, including hyper- or hypo-thyroidism (42%), rash (39%), fever (28%), leukopenia (22%), elevation of liver enzymes (19%), anorexia (17%), and fatigue (14%). Treatment–related grade 3 AEs include proteinuria (n = 1), and lipase increase (n = 2). The emergence of AEs is not dose related. JS001 PK shows dose-dependent exposure with the elimination half-life of 6 to 12 days. Among 32 evaluable pts, 1 pt have complete response (melanoma), 6 pts have partial response (3 melanoma, 2 RCC and 1 UC), and 10 pts achieve stable disease, for an ORR of 22% and a DCR of 53%. 6 out of 7 CR/PR pts still have ongoing response. Two groups of pts benefited most from JS001 treatment, pts with high tumor-infiltrating lymphocytes (TIL) (50% ORR) and pts with > 1% PD-L1 expression in tumor biopsy (46% ORR). Conclusions: JS001 exhibited a favorable safety profile in human. Treatment related AEs are in line with those from approved drugs in the same class. JS001 has demonstrated promising anti-tumor activity, especially in previously under-evaluated acral (20% ORR, 53% DCR) and mucosal (25% ORR, 50% DCR) melanomas. Clinical trial information: NCT02836795.

Early safety and efficacy from a phase I open-label clinical trial of CD137(4-1BB) agonistic antibody LVGN6051 as monotherapy and in combination with pembrolizumab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2521-2521
Author(s):  
Siqing Fu ◽  
Wael A. Harb ◽  
Sapna Pradyuman Patel ◽  
Charles Lu ◽  
Daniel M. Halperin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antitumor Activity ◽  
Safety Profile ◽  
Single Agent ◽  
Human Study ◽  
Hepatic Metastases ◽  
Preliminary Evidence ◽  
Open Label ◽  
Grade 3 ◽  
Favorable Safety

2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) with an engineered Fc capable of selectively binding to the Fcγ receptor IIB, acts as a conditional CD137 agonist, resulting in immune activation optimally in tumor microenvironment ( Qi, Nat. Commun. 2019 ). In preclinical models, LVGN6051 demonstrated robust anti-tumor efficacy and safety as a single agent and in combination with anti-PD-1 antibodies. Therefore, we have initiated this first-in-human study of LVGN6051 alone or in combination with pembrolizumab for the treatment of advanced or metastatic malignancy. Methods: This study includes accelerated dose escalation monotherapy up to 2 mg/kg of LVGN6051, and traditional 3 + 3 design for higher doses of LVGN6051 alone or in combination with pembrolizumab. Then, this study will enroll patients with specific types of malignancies following Simon’s two-stage design. Both agents are administered once every 3 weeks. Primary objectives of this study were to define the safety profile and to establish the recommended phase 2 dose (RP2D) of LVGN6051 alone or in combination with pembrolizumab. Pharmacokinetics, immunogenicity, pharmacodynamics and clinical efficacy will be also evaluated. Results: At the cut-off date on January 18, 2021, 16 subjects have been enrolled into the monotherapy cohorts (n=12, no DLT observed up to 7 mg/kg), and the combination cohort (n=4, ongoing at LVGN6051 2 mg/kg and pembrolizumab 200 mg, one DLT observed). No treatment-related adverse event (TRAE) was observed in monotherapy. Treatment-emergent adverse events (TEAE) in combination included increased ALT/AST, thrombocytopenia, and fatigue. In the combination cohort, one patient with predominant hepatic metastases and history of intermittent grade 2 hepatic impairment experienced grade 3 increased ALT/AST (DLT) on cycle 1 day 15 that were resolved to her baseline without corticosteroids on cycle 1 day 18. TRAE included increased ALT/AST, thrombocytopenia, neutropenia, nausea and fatigue. Seven of 10 evaluable patients in the monotherapy cohorts demonstrated stable disease with the longest treatment being 8+ months. Tumor reductions by >10% were observed in melanoma and neuroendocrine tumor on monotherapy. One patient with metastatic head and neck squamous cell carcinoma who had progressed on an anti-PD-L1 based therapy showed an immune partial response (iPR) for 6+ months to the combination therapy. Conclusions: Preliminary evidence showed that LVGN6051 was well tolerated and tumor shrinkages were observed. While we continue assessing its safety profile, antitumor activity was observed in the LVGN6051 and pembrolizumab cohort. The favorable safety profile and preliminary antitumor activity warrant further evaluation in patients with advanced malignancies. Clinical trial information: NCT04130542.

A phase I dose escalation study of SCB01A, a micro-tubular inhibitor with vascular disrupting activity, in patients with advanced solid tumors refractory to standard therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2531-2531 ◽  
Author(s):  
Nai-Jung Chiang ◽  
Her-Shyong Shiah ◽  
Chia-Chi Lin ◽  
Chia-Jui Yen ◽  
Hui-Jen Tsai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Solid Tumor ◽  
Safety Concern ◽  
Lower Limbs ◽  
Open Label ◽  
Dose Escalation Study ◽  
Grade 3 ◽  
Dose Levels ◽  
Vascular Disrupting

2531 Background: SCB01A is a novel anti-microtubular agent with vascular disrupting activity. The Phase I study aimed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), safety, and pharmacokinetic (PK) profiles of SCB01A in patients with advanced solid tumor. Methods: This was an open-label, phase I clinical trial with a rapid titration followed by a 3 x 3 study design. Eligible patients would receive a 3-hr intravenous infusion of SCB01A, every 21 days as one cycle. All adverse events were classified according to the CTCAE V4.0. DLT was defined as the occurrence of grade 3 with complications and grade 4 hematoloigcal, or ≥grade 3 non-hematological toxicities. Results: From June 2011 to November 2015, a total of 33 eligible patients were enrolled to eight dose levels: 2 mg/m2 (n = 1), 3 mg/m2 (n = 1), 4 mg/m2 (n = 6), 6.5 mg/m2 (n = 9, with 3 additional subjects were recruited for safety concern), 10 mg/m2 (n = 3), 16 mg/m2 (n = 3), 24 mg/m2 (n = 6) and 32 mg/m2 (n = 4). Six episodes of DLTs were observed in 5 patients (each one in dose levels of 4/6.5/24 mg/m2 and two in dose level of 32 mg/m2), including grade 4 blood creatine phosphokinase elevation (4 mg/m2), grade 3 gastric hemorrhage (6.5 mg/m2), grade 2 venous thrombosis (24 mg/m2), grade 3 peripheral neuropathy manifested as weakness of lower limbs, grade 3 aspartate aminotransferase elevation, and grade 3 hypertension (32 mg/m2). The MTD was determined to be 24 mg/m2. Pharmacokinetic profiles revealed a linear AUC-dose response with an average elimination half-life (t1/2) of 2.5 hours. Partial response was observed in one subject with buccal cancer. A total of 57.6% (19/33) subjects had stable disease for at least 2 cycles. Conclusions: SCB01A is safe and tolerable in patients with solid tumor. The MTD of SCB01A is 24 mg/m2 every 21 days, which deserves further development. Clinical trial information: NCT011159522.

AAML 1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A Report from the Children’s Oncology Group.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10003-10003 ◽  
Author(s):  
Todd Michael Cooper ◽  
Michael Absalon ◽  
Todd Allen Alonzo ◽  
Robert B Gerbing ◽  
Kasey Joanne Leger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Response Rate ◽  
Residual Disease ◽  
Complete Response ◽  
Dose Finding ◽  
Platelet Recovery ◽  
Best Response ◽  
First Relapse ◽  
Grade 3

10003 Background: Effective regimens with favorable toxicity profiles are needed for heavily pre-treated children with relapsed AML. AAML1421 is a Phase I/II study of CPX-351, a liposomal preparation of cytarabine and daunorubicin demonstrating efficacy in adults. AAML1421 sought to determine the recommended Phase 2 Dose (RPD2) of CPX-351 and the response rate (complete response (CR) + complete response without platelet recovery (CRp)) after up to 2 cycles of therapy. Methods: Children > 1 and ≤ 21 years of age with relapsed/refractory AML were eligible for dose finding, and those in first relapse were eligible for efficacy. A modified rolling six design was used for dose-limiting toxicity (DLT) assessment which occurred in Cycle 1. Dose level 1 (DL1) was 135 units/m2 on days 1, 3, and 5 with a single dose de-escalation to 100 units/m2 if DL1 was intolerable. The Efficacy Phase used a Simon-two stage design. The response rate was determined after up to 2 cycles of therapy (Cycle 1: CPX-351; Cycle 2: FLAG). The Overall Response Rate (ORR) was defined as CR+CRp+CRi (CRi = CR with incomplete hematologic recovery). Results: Thirty-eight patients (pts) enrolled: 6 in dose-finding and 32 in the efficacy phase. DLT occurred in 1/6 patients and was a grade 3 decrease in ejection fraction(EF). This was the only Grade 3 cardiac toxicity. Therefore, 135 units/m2 on days 1, 3, 5 was the RP2D. All dose finding pts were eligible for efficacy determination. One pt in the efficacy phase was unevaluable. The most common ≥ Grade 3 toxicities in Cycle 1 included fever/neutropenia (45%), infection (47%), and rash (40%). There was no toxic mortality. Best responses included 20 CR (54%), 5 CRp (14%), and 5 CRi (14%). Seventy percent achieved best response after cycle 1. Twenty-one of 25 patients with CR/CRp had no detectable residual disease (RD) (84%) by flow cytometry. HSCT was used as consolidation in 23/29 responders (79%); 18 of 23 (78%) had no detectable RD prior to HSCT. Conclusions: The RP2D of CPX-351 is 135 units/m2/dose on days 1, 3, 5. CPX-351 was well tolerated and protocol therapy was effective with CR+CRp rates of 68.3% (90% CI 52.9% to 78.0%) and ORR (CR+CRp+CRi) of 81.1% (90% CI 67.4% to 88.8%). AAML1421 response rates are superior to any published North American cooperative group clinical trial for children with AML in first relapse. Clinical trial information: NCT02642965.

Phase I trial of ALT-801, a first-in-class T-cell receptor (TCR)-interleukin (IL)-2 fusion molecule, plus gemcitabine (G) for Bacillus Calmette Guerin (BCG)-resistant non-muscle-invasive bladder cancer (NMIBC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 451-451 ◽  
Author(s):  
Guru Sonpavde ◽  
Charles Joel Rosser ◽  
Chong-xian Pan ◽  
Rahul Atul Parikh ◽  
Jeffrey Nix ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Phase I Trial ◽  
Response Assessment ◽  
Complete Response ◽  
Cell Receptor ◽  
Clinical Activity ◽  
Maintenance Cycle ◽  
Step Down ◽  
Grade 3

451 Background: Novel agents are necessary to treat BCG-resistant NMIBC to avoid radical cystectomy (RC). This phase I clinical trial evaluated the safety and activity of ALT-801, a recombinant humanized TCR-IL-2 fusion protein in BCG-resistant NMIBC. Methods: This is a Phase I trial using the 3+3 design to evaluate intravenous (IV) ALT-801 plus IV G 1000 mg/m2 in BCG-resistant high-risk NMIBC patients (pts) defined as high grade Ta, T1 or carcinoma in situ, size > 4 cm or multi-focal tumors. BCG-intolerant pts, those who refused or were unfit to undergo RC were also eligible. Initially, patients received ALT-801 monotherapy; an amendment added G. Pts received induction of 2 cycles, with a 13-day rest between cycles. Each cycle consisted of 4 doses of ALT-801 on Day 3, Day 5, Day 8, and Day 15 and 2 doses of G, one each on Day 1 and Day 8. Pts who have a biopsy-proven complete response (CR) after induction received one maintenance cycle and underwent response assessment. The initial dose of ALT-801 was 0.08 mg/kg with 2 step-down doses allowed if dose limiting toxicities (DLTs)- 0.06 mg/kg and 0.04 mg/kg. Results: 2 pts in cohort one received ALT-801 alone at 0.08 mg/kg per dose, a 3rd pt received G and ALT-801 at 0.08 mg/kg per dose. Grade ≥ 3 hepatotoxicity in the 3rd patient led to a step-down to 0.06 mg/kg dose. One pt in the 0.06 mg/kg dose experienced a DLT (Grade ≥ 3 hepatotoxicity) and the cohort was expanded to 6 pts with no further DLTs. Other attributed adverse events were: anorexia, pruritus, rash, edema, fatigue, chills. For the 0.06 mg/kg ALT-801 + G regimen, 6 pts received up to 2 cycles of induction and 4 pts received the maintenance cycle. All pts have completed therapy without further DLTs. CR was observed in 3 pts, which was durable in 2 pts lasting ≥ 18 months. Preliminarily immune studies have shown transient IFN-γ and IL-6 but not TNF-α and IL-10 induction after ALT-801 dosing. Conclusions: ALT-801 plus gemcitabine was feasible in BCG-resistant NMIBC and demonstrated immune responses and potential durable clinical activity. Further evaluation in expansion cohorts in a phase Ib/II trial is planned. Clinical trial information: NCT01625260.

Final Results Of a Phase II Study Of Lenalidomide In Combination With Rituximab For The Treatment Of Indolent Non Follicular Non Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4383-4383 ◽  
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Marina Cesaretti ◽  
Luigi Marcheselli ◽  
Gabriele Buda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Informed Consent ◽  
Phase Ii ◽  
Conflicts Of Interest ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Open Label ◽  
Grade 3

Abstract Background Advanced-stage, relapsed indolent non follicular lymphomas (INFLs) have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Thus, there is a need for innovative treatment with high efficacy and a good safety profile. Lenalidomide (R®) is an immunomodulatory drug with a direct tumoricidal effect and action on T, NK and stromal cells that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL. Methods Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R® 20 mg once daily on days 1-21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R® when given in combination with R and to assess the safety of R2 regimen evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were the evaluation of progression free survival (PFS) and overall survival (OS). Results From July 2010 and March 2013, 44 pts entered the protocol. Six out of 44 pts were excluded from this analysis as 2 withdrew informed consent and 4 refused to start treatment immediately after signing the informed consent. Enrolled pts (38 cases) had: 18 small lymphocytic lymphoma (SLL), 12 lymphoplasmacytic lymphoma (LPL) and 8 marginal zone lymphoma (MZL). Median age was 68 years (51-75) and 58% were male. LDH value was increased in 21% of pts and β-2-microglobulin in 75%; 51% of pts had Hb<12 g/dL and 66% had bone marrow involved (median infiltrating 40%). Of the 38 pts, 7 achieved a complete remission and 14 a partial remission with an ORR of 55%. Seven pts had a stable disease and 5 a lymphoma progression. In general, the regimen R2 was relatively well-tolerated. Grade 3-4 hematological events were observed in 22 pts. The most common adverse events were neutropenia (58%), thrombocytopenia (11%), anemia (10%) and infection (10%). Grade 3-4 non hematological events were fever (5%), dyspnea (3%), allergic reaction to R (3%), renal failure (3%) and erythema (3%). Growth factors were administered in 58% of pts. The median dose intensity was 0.94 for R and 0.98 for R®. With a median follow-up of 19 months (range 1-43), overall 6 pts died, 5 for lymphoma progression and 1 for treatment related toxicity. The 2-years OS and the 2-years PFS were shown in Figure 1. Figure 2 shows the PFS by histology. The percentage of 2-years PFS (71%) for MZL appear impressive. Conclusions The chemo-free R2 scheme as treatment for relapse INFLs produces response in about 50% of pts and remission appear durable in pts with MZL. The toxicity profile of the combination is tolerable with manageable hematologic side effects. These results support the design of clinical trial with this chemo-free combination as first line treatment for INFLs, in particular for MZL. Disclosures: No relevant conflicts of interest to declare.

PREDIX II HER2: Improving pre-operative systemic therapy for human epidermal growth factor receptor 2 (HER2) amplified breast cancer (BC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS605-TPS605
Author(s):  
Renske Kornalijnslijper-Altena ◽  
Anne Andersson ◽  
Yvonne Brandberg ◽  
Luisa Edman Kessler ◽  
Ellinor Elinder ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Predictive Marker ◽  
Complete Response ◽  
Clinical Trial Registry ◽  
Open Label

TPS605 Background: Neo-adjuvant systemic therapy (NAT) is the standard of care for most patients with early HER2-amplified and triple negative breast cancer (BC). Increasing the rate of pathological complete response (pCR) is highly meaningful for those patients, as pCR is strongly predictive for improved long-term disease-related outcomes. Clinical and preclinical evidence support the hypothesis that pCR-rates may be augmented by the addition of checkpoint inhibitors, such as monoclonal antibodies targeting the Programmed Death Ligand receptor 1 (PD-L1), to standard systemic NAT. Studies in different BC patient cohorts (e.g., IMPassion130, PANACEA, KATE2) have indicated that PD-L1 protein expression on tumor-infiltrating lymphocytes (TIL’s) is a predictive marker for checkpoint inhibitor efficacy. Methods: We have initiated a phase II open-label, 2:1 randomized clinical trial where women with early HER2-amplified, PD-L1+ BC (cT2-3 and/or cN+) are treated with standard NAT (composed of anti-HER2 antibodies with a chemotherapy backbone of sequentially taxanes + carboplatin and epirubicin + cyclophosphamide [EC]) +/- atezolizumab during EC. N = 190 patients will be accrued in nine centers in Sweden to be able to demonstrate a 20% increase in pCR-rate, with a power of 80% and a two-sided alpha of 10%. Firstly, a prescreening is performed to select patients with a PD-L1 expression of > 1% on TIL’s. Important exclusion criteria are significant organ dysfunction and (with some exceptions) active auto-immune diseases. Extensive translational side-studies are performed to explore predictive markers for treatment efficacy, including clinicopathologic studies, molecular imaging and microbiome analyses, as well as monitoring of acute and chronic treatment-related toxicity, objective cognitive function and quality of life. As of February 11th, 4 patients have been prescreened and 1 enrolled in the trial. The clinical trial registry number is NCT03894007. Clinical trial information: NCT03894007 .

804 A phase II study of the anti-programmed cell death-1 (PD-1) antibody penpulimab in patients with metastatic nasopharyngeal carcinoma (NPC) who had progressed after two or more lines of chemotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A853-A853
Author(s):  
Xiaozhong Chen ◽  
Wei Wang ◽  
Qingfeng Zou ◽  
Jingao Li ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Disease Progression ◽  
Receptor Occupancy ◽  
Complete Response ◽  
Hepatic Function ◽  
Open Label ◽  
Barr Virus ◽  
Duration Of Response ◽  
Epstein Barr ◽  
Grade 3 ◽  
Anti Tumor Activity

BackgroundNPC is rare but has a distinct geographic distribution, with a predominance in Southeast Asia. Favorable results with PD-1 inhibitors in NPC provide a strong rationale to investigate penpulimab in this disease. Penpulimab was engineered to eliminate FcγR binding and ADCC/ADCP completely,where ADCC/ADCP effects can induce T-cell apoptosis and clearance and then compromise anti-tumor activity. Penpulimab demonstrated a slower PD-1 antigen binding off-rate than marketed PD-1 antibodies, which result in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody and may contribute to slower binding off-rate. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of penpulimab.MethodsAK105-202 (NCT03866967) is a multicenter, single-arm, open-label study of penpulimab in metastatic NPC patients (pts) with disease progression after ≥2 prior lines of therapy including platinum-containing chemotherapy. All patients received penpulimab 200 mg q2w until progression or unacceptable toxicity. The primary endpoint was ORR based on RECIST v1.1 as assessed by an independent review committee (IRC). Key secondary endpoints included DCR, PFS, duration of response (DoR). Archived tissues were retrieved for the analysis of PD-L1 (Shuwen SAB-028). PD-L1 expression of tumor proportion score (TPS)≥50% was regarded as positive. Plasma Epstein-Barr virus DNA were obtained for biomarker correlative analysis.ResultsAs of 18 September 2020, the median follow-up was 7.9 months (range 0.9 to 16.9). The anti-tumor activity of penpulimab in the 111 pts with disease progression after ≥2 prior lines of therapy evaluable for efficacy (defined as pts who had an opportunity to be followed for at least 16 weeks and had measurable disease at baseline per RECIST v1.1) is shown in the table 1.Treatment-related adverse events (TRAEs, including unlikely related) occurred in 79.2% of pts (≥G3 in 14.6% [19/130], treatment discontinuation in 3.1% [4/130]). Treatment-related SAEs occurred in 10.0% [13/130]. Most frequent TRAEs (≥10%) were fever (24.5%), hypothyroidism (24.6%), anemia (23.1%), ALT increased (17.0%) and WBC decreased (10.8%). Grade ≥3 TRAEs (≥2%) were hepatic function abnormal (2.3%) and anemia (2.3%).Abstract 804 Table 1a. Including 1 complete response and 29 partial response. At data cutoff, 90% of responders remained ongoing.b.43 pts were PD-L1 positive (TPS≥50%) and 66 pts were PD-L1 negative (TPS<50%).c. Including 1 ongoing response awaiting confirmation classified under SD.ConclusionsPenpulimab demonstrated encouraging anti-tumor activity and favorable safety profile in pts with disease progression after ≥2 prior lines of therapy. A higher proportion of objective responses was observed in NPC pts with PD-L1–positive tumors receiving penpulimab than those with PD-L1–negative tumors.

scholarly journals DIPG-52. PHASE I CLINICAL TRIAL OF ONC201 IN PEDIATRIC H3 K27M-MUTANT GLIOMA OR NEWLY DIAGNOSED DIPG

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii297-iii297
Author(s):  
Sharon Gardner ◽  
Rohinton Tarapore ◽  
Jeffrey Allen ◽  
Wafik Zaky ◽  
Yazmin Odia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Phase I ◽  
Single Agent ◽  
High Grade Glioma ◽  
Newly Diagnosed ◽  
Liquid Formulation ◽  
Open Label ◽  
Dismal Prognosis ◽  
Expansion Cohort

Abstract H3 K27M-mutant gliomas often manifest as midline gliomas, have a dismal prognosis, and have no effective treatments. ONC201 efficacy has been shown in high-grade glioma preclinical models and durable responses with single agent ONC201 have been reported in adults with recurrent H3 K27M-mutant gliomas. These observations led to a Phase I pediatric clinical trial of ONC201 dosed by body weight. This multi-center, open-label, 3 + 3 dose-escalation and dose-expansion clinical trial (NCT03416530) for H3 K27M-mutant glioma or non-biopsied DIPG has 6 arms: arms A and E determine the RP2D in pediatric post-radiation (recurrent or not-recurrent) H3 K27M-mutant glioma patients with ONC201 administered as an oral capsule as well as a liquid formulation, respectively. Both arms have completed accrual. The study is currently enrolling newly diagnosed DIPG patients to determine the RP2D for ONC201 in combination with radiation (arm B). Dedicated assessment of intratumoral ONC201 concentrations in midline gliomas patients (arm C) and the effects of ONC201 in H3K27M DNA levels in circulating CSF (arm D) are currently enrolling patients. ONC201 as a single agent in patients with progressive H3K27M mutant tumors following irradiation (excluding DIPG/spinal cord tumors) was recently opened (arm F). Once the RP2D is confirmed, there is a dose-expansion cohort to confirm the safety, radiographic efficacy and survival with ONC201. The primary endpoints of arms A, B, and E have been established with the RP2D of 625mg scaled by body weight as a capsule or liquid formulation administered alone or in combination with radiation without incidence of dose-limiting toxicity.

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