Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced/metastatic melanoma resistant to anti-PD-1/PD-L1 therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9555-9555 ◽  
Author(s):  
Asim Amin ◽  
Mohammed M. Milhem ◽  
Georgina V. Long ◽  
Christopher J. Hoimes ◽  
Theresa Michelle Medina ◽  
...  
Keyword(s):  
Ct Scan ◽  
Phase 2 ◽  
Open Label ◽  
Prior Therapy ◽  
Phase 2 Trial ◽  
Ifn Alpha ◽  
Unresectable Stage ◽  
Injection Methods ◽  
Grade 3 ◽  
Antigen Presenting

9555 Background: SD-101 is a synthetic CpG-ODN agonist of TLR9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells - activating T cell anti-tumor responses. Pembrolizumab has demonstrated activity in melanoma. SYNERGY-001/KEYNOTE-184 study assesses the safety and preliminary efficacy of the combination of intratumoral SD-101 and intravenous pembrolizumab in PD1/PDL 1 resistant unresectable stage IIIC- IV melanoma. A prior phase 2 study with SD-101 at 8 mg per injection resulted in a 21.4% ORR in this population (Abstract 3781, ESMO 2018). We report preliminary data in this ongoing phase 2 trial evaluating efficacy at a lower SD-101 dose of 2 mg per injection. Methods: PD1/PDL 1 resistant melanoma patients received 2 mg of SD-101 intratumorally per lesion in 1-4 lesions (weekly x 4 doses followed by Q3W x 7). Pembrolizumab was administered at a dose of 200 mg intravenously Q3W. Scans were performed Q9W. Responses were assessed per RECIST v1.1. Results: 23 patients have been enrolled with baseline characteristics: median age 65 years; male: 77%; stage at screening: IIIC = 26%; IV = 57%, unknown = 17%; LDH > ULN: 36%. Lines of prior therapy: 1: 52%; 2: 22%; > 2: 26%. Prior anti CTL-A4 therapy: 39%. Best overall response on prior antiPD-1/PD-L1: PD: 88%, PR/CR: 8%, SD: 4%. Safety: Grade ≥3 treatment-related AEs: pneumonia and constipation (8%). No immune-related AEs reported. 2 non-treatment related SAEs reported from 2 patients: pneumonia and intussusception. 4 patients discontinued treatment early: 1 post SAE, per patient’s request, 3 due to PD. 1 patient died due to malignant pleural effusion after 1 dose of SD 101 and Pembrolizumab. No treatment related deaths. Efficacy: Mean duration on treatment: 39 days (1 - 169). mITT population: six patients at time of first CT scan at day 64: PR: 1, SD: 1, PD:3; non-evaluable: 1. 17 patients on study have not yet had first CT scan. Conclusions: The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab is well tolerated. Mature efficacy data, with additional first and second follow-up CT scans, will be presented at the meeting. Clinical trial information: NCT02521870.

Phase 1b/2, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6039-6039 ◽  
Author(s):  
Ezra E.W. Cohen ◽  
Lisle Nabell ◽  
Deborah J.L. Wong ◽  
Terry A Day ◽  
Gregory A. Daniels ◽  
...  
Keyword(s):  
Ct Scan ◽  
Open Label ◽  
Primary Tumors ◽  
Ifn Alpha ◽  
Hpv Status ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Ecog Ps ◽  
Antigen Presenting

6039 Background: SD-101, a synthetic CpG-ODN agonist of TLR9, stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells - activating T cell anti-tumor responses. Pembrolizumab has demonstrated activity in HNSCC. Study DV3-MEL-01 (NCT02521870) assesses safety and efficacy of SD-101 in combination with pembrolizumab in patients with recurrent/metastatic HNSCC. We have previously reported a 27.3% ORR in 22 patients receiving 8 mg SD-101/injection in the modified ITT after at least 2 CT scans due to late responses (Abstract 3560, ESMO 2018). Higher efficacy at a lower SD-101 dose, 2 mg/injection, has been reported in advanced melanoma patients (LBA 45, ESMO 2018). Consequently, this dose is now being assessed in HNSCC. We report preliminary data with the 2 mg/injection dose in 23 patients in mITT at the first CT scan. Methods: Anti-PD-1/PD-L1 naïve patients received 2 mg SD-101 intratumorally in 1 - 4 lesions (weekly x 4 doses then Q3W x 7 doses). Pembrolizumab is was administered IV at 200 mg Q3W. Responses were assessed per RECIST v1.1. Results: 28 patients enrolled: median age 63 y/o, male 68%; ECOG PS 0-1 (18%/82%); mean prior lines of systemic therapy 1 (0-3); mean treatment duration 70 days (1-253). Primary tumors: 19 (68%) oropharyngeal; 3 (10%) laryngeal; 2 (7%) hypopharyngeal; 4 (14%) unknown. Mean number of target lesions: 1.82 (1 to 5). HPV status: 7 (25%) +, 9 (32%) -, 12 (43%) unknown. 18 (64 %) discontinued treatment: 12 (42%) due to PD, 4 (16%) deaths, 1 (3%) consent withdrawn, 1 (3%) went to hospice. Mean follow up 2.70 months. Safety: 16 non-treatment-related SAEs in 9 patients. 2 treatment-related Grade ≥3 AEs: sepsis (4%) and lymphopenia (4% ). No treatment-related deaths. Efficacy: 23 patients in the mITT population with first CT scan at day 64: ORR: CR: 2, PR: 3 (22%); SD: 6 (26%), PD: 7 (30%), non-evaluable: 5 (22%). Disease control rate (48%). 5 patients on study have not had a CT scan. Conclusions: SD-101 with Pembrolizumab shows early promising data and is well tolerated. Additional follow-up scans from both dose cohorts are being evaluated and will be presented. Clinical trial information: NCT02521870.

Phase 1b/2, open label, multicenter, study of intratumoral SD-101 in combination with pembrolizumab in anti-PD1 naïve & experienced metastatic melanoma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9550-9550 ◽  
Author(s):  
Abraham C.F. Leung ◽  
Shivaani Kummar ◽  
Sanjiv S. Agarwala ◽  
John J. Nemunaitis ◽  
Rene Gonzalez ◽  
...  
Keyword(s):  
Injection Site ◽  
Metastatic Melanoma ◽  
Stage Iv ◽  
Low Grade ◽  
Open Label ◽  
Ifn Alpha ◽  
Tumor Lesion ◽  
Grade 3 ◽  
The Individual ◽  
Antigen Presenting

9550 Background: SD-101 is a synthetic CpG-ODN agonist of TLR 9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells to activate T cell anti-tumor responses. Pembro is a PD-1 inhibitor approved for the treatment of metastatic melanoma. This study, MEL-01 (NCT02521870), assesses the safety and preliminary efficacy of SD-101 in combination with pembro in stage IIIC-IV melanoma. Methods: A modified 3+3 design was used for SD-101 dose escalation of 1, 2, 4, and 8 mg injected in a single tumor lesion Q1W x 4 then Q3W x 7 in combination with pembro (200 mg IV Q3W). Tumor responses were assessed per investigator using RECIST v1.1. Results: In phase Ib, 22 pts were enrolled: median age 64 y/o, male 68%, white 82%, Stage IV/IIIc 86%/14%, LDH > 1 ULN 27%, ≥ 3 prior lines therapy 36%, anti-PD-1 naïve (n = 9) and experienced (n = 13). There has been no dose limiting toxicity (DLT) to date. The most common (≥20%) treatment-related AEs (TRAEs) were transient low-grade fatigue, myalgia, headache, chills and injection site reactions. Grade ≥ 3 TRAEs were observed in 59.1% pts (most common: myalgia 13.6% and injection site pain 13.6%). Immune-related AEs occurred in 2 pts. One had a G2 pneumonitis on Day 23 resulting in drug withdrawal and the other G3 hypophysitis (85 days after last treatment). No deaths occurred. Responses were observed at all doses in PD-1 inhibitor naïve pts, both at the injected and non-injected lesions. A response was seen at the 8 mg dose in PD-1 inhibitor experienced pts. With median f/u of 97 days (max 382), the ORR was 66.7% in the PD-1 inhibitor naïve patients with best overall response of CR 22.2% (n = 2), PR 44.4% (n = 4), SD 11.1% (n = 1), PD 11.1% (n = 1), and NE 11.1% (n = 1). In the PD-1 inhibitor experienced pts: PR 7.7% (n = 1) and SD 38.5% (n = 5). Conclusions: The combination of SD-101 and pembro was well tolerated and demonstrates no worsening of the expected toxicities of each of the individual monotherapies. These interim data support enhanced activity of adding SD-101 to pembro in anti-PD-1 naive metastatic melanoma as well as potential activity in anti-PD-1 experienced pts. Additional follow up data through May 15, 2017 will be presented. Clinical trial information: NCT02521870.

KEYNOTE-799: Phase 2 trial of pembrolizumab plus platinum chemotherapy and radiotherapy for unresectable, locally advanced, stage 3 NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8512-8512
Author(s):  
Salma K. Jabbour ◽  
Ki Hyeong Lee ◽  
Nicolaj Frost ◽  
Valeriy Vladimirovich Breder ◽  
Dariusz M. Kowalski ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Phase 2 ◽  
Open Label ◽  
Tumor Histology ◽  
Phase 2 Trial ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Carboplatin Auc

8512 Background: KEYNOTE-799 (NCT03631784) is an ongoing study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC. Prior results from this study in a subset of pts (primary efficacy population) showed an ORR of 69.6% in cohort A (squamous and nonsquamous, n = 112) and 70.5% in cohort B (nonsquamous, n = 61), and grade ≥3 pneumonitis in 8.0% and 7.9% of pts, respectively. Here, we present results for all pts enrolled in KEYNOTE-799. Methods: This nonrandomized, multisite, open-label phase 2 trial enrolled pts aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA‒C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received 1 cycle of carboplatin AUC 6 and paclitaxel 200 mg/m2 and pembro 200 mg. After 3 wks, pts received carboplatin AUC 2 and paclitaxel 45 mg/m2 QW for 6 wks and 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2,and pembro 200 mg Q3W, and TRT in cycles 2 and 3. All pts received an additional 14 cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Efficacy and safety were assessed in all pts as-treated. Results: Of 216 pts enrolled in KEYNOTE-799 (cohort A, n = 112; cohort B, n = 104), 112 in cohort A and 102 in cohort B received treatment. As of October 28, 2020, the median (range) time from first dose to database cutoff was 18.5 (13.6–23.8) mo in cohort A and 13.7 (2.9–23.5) mo in cohort B. ORR (95% CI) was 70.5% (61.2%‒78.8%) in cohort A and 70.6% (60.7%‒79.2%) in cohort B. Median DOR was not reached in either cohort (Table). ORR was similar regardless of PD-L1 status ([TPS <1% and TPS ≥1%]; Cohort A, 66.7% and 75.8%; Cohort B, 71.4% and 72.5%) and tumor histology (Cohort A, squamous, 71.2% and nonsquamous, 69.2%). Grade ≥3 pneumonitis occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3‒5 treatment-related AEs occurred in 72 pts (64.3%) in cohort A and 51 (50.0%) in cohort B. Conclusions: Pembro plus cCRT continues to demonstrate promising antitumor activity, regardless of PD-L1 TPS and tumor histology, and manageable safety in pts with previously untreated, locally advanced, stage III NSCLC with longer follow-up. Clinical trial information: NCT03631784. [Table: see text]

scholarly journals Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study

Blood ◽  
2020 ◽  
Vol 135 (18) ◽  
pp. 1541-1547 ◽  
Author(s):  
Vaishali Sanchorawala ◽  
Shayna Sarosiek ◽  
Amanda Schulman ◽  
Meredith Mistark ◽  
Mary Ellen Migre ◽  
...  
Keyword(s):  
Median Time ◽  
Respiratory Infections ◽  
Renal Involvement ◽  
Cardiac Response ◽  
High Dose ◽  
Al Amyloidosis ◽  
Phase 2 ◽  
Prior Therapy ◽  
Phase 2 Trial ◽  
Grade 3

Abstract Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, and hematologic and clinical response. Daratumumab 16 mg/kg was administered by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter until progression or unacceptable toxicity, for up to 24 months. Twenty-two patients with previously treated AL amyloidosis were enrolled. The majority of the patients had received high-dose melphalan and stem cell transplantation and/or treatment with a proteasome inhibitor. The median time between prior therapy and trial enrollment was 9 months (range, 1-180 months). No grade 3-4 infusion-related reactions occurred. The most common grade ≥3 adverse events included respiratory infections (n = 4; 18%) and atrial fibrillation (n = 4, 18%). Hematologic complete and very-good-partial response occurred in 86% of patients. The median time to first and best hematologic response was 4 weeks and 3 months, respectively. Renal response occurred in 10 of 15 patients (67%) with renal involvement and cardiac response occurred in 7 of 14 patients (50%) with cardiac involvement. In summary, daratumumab is well tolerated in patients with relapsed AL amyloidosis and leads to rapid and deep hematologic responses and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT02841033.

Phase II study of pembrolizumab plus capecitabine and bevacizumab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Interim analysis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 77-77
Author(s):  
Andrea Grace Bocobo ◽  
Renee Wang ◽  
Spencer Behr ◽  
Julia C. Carnevale ◽  
Pelin Cinar ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Phase 2 ◽  
Open Label ◽  
Eligibility Criteria ◽  
Stage Design ◽  
Phase 2 Trial ◽  
Best Response ◽  
Grade 3 ◽  
Clinical Trial Information ◽  
Therapy Treatment

77 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. We present results at the planned interim analysis. Methods: Design:single-arm, open-label, single-site phase 2 trial with a safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts. Per the Simon’s 2-stage design, ≤1 response in 29 patients (pts) requires trial suspension. Key eligibility criteria: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: RP2D PO capecitabine on days 1-14 plus 200 mg IV pembrolizumab and 7.5 mg/kg IV bevacizumab on day 1 in 21-day cycles. Pts are followed for toxicity and radiographic response. Results: From 04/2018-09/2020, 29 pts were enrolled, of whom 15 (52%) were female; 21 (72%) white; and median age was 55 years (range 36-77 years). Prior therapies: 2 (7%) pts had SD and 27 (93%) pts had PD on fluoropyrimidine-containing regimens; 24 (83%) pts had prior exposure to bevacizumab. The RP2D for capecitabine was 1000 mg/m2 PO BID, with no dose limiting toxicities observed. Complete toxicity data are available for 25 off-treatment pts. The most common related adverse events (AEs) were palmar-plantar erythrodysesthesia (PPE) (64%) and fatigue (68%). Grade ≥3 related AEs occurred in 9 (36%) pts, including immune-related AEs of Grade 3 dyspnea, hypophosphatemia, and pancreatitis in 1 pt each. Treatment related AEs leading to dose interruptions, reductions, or delays occurred in 15 (60%) pts, most commonly PPE in 13 (52%) pts. No pt had a related AE leading to treatment discontinuation or death. Disposition: of 29 pts enrolled, 24 were removed for PD and 1 was removed for an unrelated AE. Best response by RECIST 1.1 in 23 evaluable pts: partial response (PR) in 2 (9%); SD in 14 (61%); PD in 7 (30%). Median time on treatment was 6 months (range 2-26 months). Conclusions: Combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. With 2 responses, the study met interim analysis criteria to continue accrual. Tissue and blood-based immune correlatives are planned. Clinical trial information: NCT03396926.

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