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American Society of Clinical Oncology (ASCO)

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Relmacabtagene autoleucel (relma-cel; Carteyva) elicited durable responses and a high overall survival (OS) rate in Chinese patients with relapsed/refractory large B-cell lymphoma (LBCL), according to 2-year follow-up data from the phase 2 RELIANCE trial (NCT04089215) presented during the 2022 ASCO Annual Meeting.

At a median follow-up of 24 months (95% CI, 23.9-24.1) , the best overall response rate (ORR) achieved with the autologous CD19-targeted CAR T-cell therapy was 77.6% among 58 evaluable patients, which included a complete response (CR) rate of 53.5%. The median duration of response (DOR) was 20.3 months (95% CI, 4.86–not estimable [NE]), and the 2-year DOR rate was 40.3%.

Moreover, the median progression-free survival (PFS) with the therapy was 7 months (95% CI, 4.76-24.15), and the median OS was not yet reached. The 2-year PFS and OS rates were 38.8% and 69.3%, respectively.

“Relma-cel demonstrated durable responses with a high 2-year overall survival [OS] rate,” lead study author Zhitao Yang, MD, of the Department of Lymphoma and Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) of Peking University Cancer Hospital & Institute in Beijing, China, and colleagues, wrote in a poster presentation of the data. “The median OS has not yet been reached for responding patients, and [there was] a manageable safety profile.”

RELIANCE was the first study of a CD19-directed CAR T-cell therapy to receive investigational new drug approval by the China National Medical Products Administration. Prior results from the study showed high response rates and low toxicity with relma-cel.

The study enrolled patients who were 18 years or older with histologically LBCL who received at least 2 prior lines of therapy. Patients were required to have an ECOG performance status of 0 or 1, an accessible PET-positive lesion, a measurable CT-positive lesion, adequate organ function, and acceptable vascular access for leukapheresis.

 Those who received prior CD19-targeted therapy needed to confirm that their lesions still expressed CD19.

Key exclusion criteria included central nervous system (CNS)–only involvement, a history of another primary malignancy that has not been in remission for at least 2 years, or any history of a serious cardiovascular disease, among others.

Fifty-nine adult patients were randomized to receive relma-cel at 100 x 10

 CAR-positive T cells. Prior to CAR T-cell infusion, all patients received lymphodepleting chemotherapy, and some received bridging chemotherapy.

The primary end point of the study was 3-month ORR. Secondary end points included 3-month CR rate, DOR, PFS, OS, and safety.

Additional data showed that among evaluable patients who received relma-cel at 100 x 10

 CAR-positive T cells (n = 21), the median DOR was 23.3 months (95% CI, 5.16-NE). Those who were administered the therapy at 150 x 10

 CAR-positive T cells (n = 24), experienced a median DOR of 6.0 months (95% CI, 2.99-NE).

In patients who received relma-cel at 100 x 10

 CAR-positive T cells (n = 27), the median PFS was 8.8 months (95% CI, 5.55-NE). For those who received the therapy at 150 x 10

 CAR-positive T cells (n = 31), the median PFS was 5.5 months (95% CI, 2.96-21.19).

Regarding safety, 91.5% of patients experienced at least 1 treatment-related adverse effect (TRAE) with relma-cel, and 55.9% had at least 1 effect that was grade 3 or higher in severity. Any-grade cytokine release syndrome (CRS) and neurotoxicity occurred in 47.5% and 20.3% of patients, respectively; these effects were grade 3 or higher in 5.1% and 3.4% of patients, respectively.

The median duration of any-grade CRS was 7 days (range, 1-118), and the median time to CRS was 4 days (range, 1-10). The median duration of any-grade neurotoxicity was 12.5 days (range, 1-49), and the median duration of neurotoxicity was 8.5 days (range, 2-11).

The other most common grade 3 or higher TRAEs included neutropenia (40.7%), leukopenia (22%), lymphopenia (11.9%), thrombocytopenia (11.9%).

Although relma-cel has shown to have manageable safety and to produce substantial durable responses in this population, further follow up is needed, according to the study authors.

Ying Z, Song Y, Yang H, et al. Two-year follow-up result of RELIANCE study, a multicenter phase 2 trial of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma. 

. 2022;40(suppl 16):7529. doi:10.1200/JCO.2022.40.16_suppl.7529

CD19-targeted CAR T cells for relapsed and refractory (R/R) non-Hodgkins lymphoma. ClinicalTrials.gov. Updated January 22, 2021. Accessed August 17, 2022. 

https://clinicaltrials.gov/ct2/show/NCT04089215

At a median follow-up of 24 months, the best ORR achieved was 77.6% among 58 evaluable patients with large B-cell lymphoma treated with relma-cel. 

Long-Term RELIANCE Trial Data Shows Durability With Relma-Cel in LBCL

"We had a workshop where we got all the different sponsors and stakeholders together and sort of talked about some of these issues with the overreach or the redundancy of some of these issues with starting up cell therapies, and I think there's still lots of work to be done.”

The 2022 American Society of Clinical Oncology (ASCO) meeting was held both virtually and in Chicago, Illinois, on June 3-7, 2022. One focus of the meeting was chimeric antigen receptor (CAR) T-cell therapies, their current impact in different cancers, and further research that remains to be done to improve them.

During the meeting, Melissa Alsina, MD, gave a talk on novel CAR therapies, targets, and approaches in multiple myeloma at ASCO focused on idecabtagenevicleucel (ide-cel) and some investigative therapies. Alsina is an associate professor of medicine at the Blood and Marrow Transplant Program and head of the Multiple Myeloma Transplant Program at Moffitt Cancer Center.

CGTLive spoke with Frederick Locke, MD, to gain additional perspective on CAR T-cell therapies in the field. Locke serves as the vice-chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt. He discussed managing toxicities and the potential of outpatient administration in the future. He also commented on the need to improve the process of starting cell therapies in centers.

Alsina M. The road not yet taken: Novel CARS and newer horizons. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022.

The vice-chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center discussed more work to be done with CAR T-cell therapies. 

Frederick Locke, MD, on Further CAR T Research 

“I’m really excited about the impact and the potential of CAR T-cell therapies, these are still treatments that can cause toxicity and are still administered in specialized treatment centers, but as we get a better grasp of the risk factors for toxicities and management, we will be able to administer these treatments at more centers closer to patients and where they live."

2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, held both virtually and in Chicago, Illinois,

 was on chimeric antigen receptor (CAR) T-cell therapies, their current impact in different cancers, and further research that remains to be done to improve them.

Melissa Alsina, MD, associate professor of medicine, Blood and Marrow Transplant Program, and head, Multiple Myeloma Transplant Program, Moffitt Cancer Center, gave a talk on novel CAR therapies, targets, and approaches in multiple myeloma at ASCO focused on idecabtagene vicleucel (ide-cel) and some investigative therapies.

To gain additional perspective on CAR T-cell therapies in the field, 

spoke with Frederick Locke, MD, the vice-chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy, also of Moffitt Cancer Center, to learn more about the impact potential of CAR T-cell therapies in hematologic malignancies. He discussed positive outcomes seen so far with CAR T-cell therapies, including tisa-cel, liso-cel, ide-cel, cilta-cel, and brexu-cel.

The vice-chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center discussed positive data seen with tisa-cel, liso-cel, ide-cel, cilta-cel, and brexu-cel. 

Frederick Locke, MD, on the Impact Potential of CAR T-Cell Therapies in Hematologic Malignancies 

In patients with previously treated advanced gastric/gastroesophageal junction adenocarcinoma, chimeric antigen receptor-modified autologous T cells targeting Claudin18.2 (CLDN18.2) (CT041, CARsgen Therapeutics) had a manageable safety/tolerability profile and promising efficacy, according to preliminary data from an ongoing phase 1b/2 study (NCT04581473).

2022 American Society of Clinical Oncology (ASCO) Annual Meeting

, which is taking place from June 3-7 in Chicago, by Changsong QI, MD, PhyD, of Peking University Cancer Hospital & Institute in China.

 is a promising therapeutic target that is often expressed in gastric/gastroesophageal junction cancer. CT041 autologous CAR T-cell injection has shown promising anti-tumor activity in preclinical studies, while results from phase 1 trial suggested that CT041 was well tolerated and had encouraging efficacy in previously treated patients with CLDN18.2-positive advanced gastric/gastroesophageal junction adenocarcinoma. Data from a companion US-based study (NCT04404595) elicited either a response or stable disease in a majority of heavily pretreated patients with CLDN18.2-positive advanced gastric and pancreatic adenocarcinoma, 

results of which were also presented at ASCO 2022

In this open-label, multicenter, phase 1b/2 trial, the researchers assessed the safety, tolerability, and efficacy of CT041 in 14 patients with previously treated CLDN18.2-positive advanced gastric/gastroesophageal junction adenocarcinoma. There are 2 stages in the ongoing study. The phase 1b stage is a dose escalation and dose expansion study and the phase 2 stage is to verify the efficacy and safety of CT041 treatment.

From November 2020 to May 2021, a total of 14 patients (medium age 44.5) with gastric/gastroesophageal junction adenocarcinoma cancer were enrolled in phase 1b. Of the patients, 85.7% had received 2 prior lines of treatment and 14.3% had at least 3 lines. Meanwhile, 57.1% had at least 3 metastatic organs, 92.9% had peritoneal dissemination, and 64.3% had signet ring cell carcinoma. For up to 3 doses of the autologous CAR T-cell injection infusion, 3 of the patients received 3.75 × 10

The most reported adverse events of grade 3 or higher were hematologic toxicity related with lymphodepletion. No dose-limiting toxicities, treatment-related death, neurologic toxicity, or gastrointestinal toxicities were observed. Most occurrences of cytokine release syndrome (CRS) were grade 1 or 2, and 1 patient experienced grade 4 CRS and fully recovered.

Of the patients, 57.1% achieved partial response, 14.3% showed stable disease. With a median follow-up of 8.9 months (95% CI 5.91, NE), the median progression-free survival (PFS) was 5.6 months (95% CI 1.9, 7.4), and median overall survival was 10.8 months (95% CI 5.1, NE). Seven patients were still alive at last follow-up.

This study is ongoing with further investigation of CT041 in phase 2 underway. CARsgen Therapeutics announced in March that the Center for Drug Evaluation of the National Medical Products Administration of China approved the initiation of the CT041 confirmatory phase 2 study.

“The treatment options for gastric cancer patients who have failed at least 2 prior lines are very limited. The median progression-free survival of available therapies, including anti-PD-1 monoclonal antibody, is merely about 2 months, indicating an urgent unmet medical need for more innovative and effective drugs,” said Lin Shen, MD, of Beijing Institute for Cancer Research, the principal investigator. In this early study of CT041 led by our center, themedium “PFS of CT041 was over 5 months, which is very promising data.”

1. QI C, Liu C, Gong J, et al.Safety, tolerability, and preliminary efficacy results in patients with advanced gastric/gastroesophageal junction adenocarcinoma from a phase Ib/II study of CLDN18.2 CAR T-cell therapy (CT041). Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #4017

2. Claudin18.2 CAR T Cells (CT041) Receives Approval to Initiate A Confirmatory Phase II Clinical Trial for advanced GC/GEJ in China. News release. CARsgen Therapeutics, March 3,2022. 

https://www.prnewswire.com/news-releases/claudin18-2-car-t-cells-ct041-receives-approval-to-initiate-a-confirmatory-phase-ii-clinical-trial-for-advanced-gcgej-in-china-301494828.html

The chimeric antigen receptor-modified autologous T cells targeting CLDN18.2 had a manageable safety/tolerability profile and promising efficacy.

CARsgen Therapeutics’ CT041 Shows Promise in Advanced Gastric/Gastroesophageal Junction Adenocarcinoma 

 first-in-class allogeneic gamma delta (γδ) chimeric antigen receptor (CAR) T-cell therapy, was well-tolerated with encouraging preliminary efficacy in patients with B-cell malignancies.

New data on ADI-001 from a phase 1 trial (NCT04735471) were presented by Sattva S. Neelapu, MD, department of lymphoma and myeloma, division of cancer medicine, University of Texas MD Anderson Cancer Center, at the 

2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, held both virtually and in Chicago, Illinois.

“As compared with conventional αβ T-cells, γδ CAR T-cells may provide 3 mechanisms of anti-tumor activity, thus potentially limiting the ability for tumor escape. First, they provide innate anti-tumor activity targeting multiple surface proteins selected by evolution to mark tumors for cell killing. Second, they have adaptive anti-tumor activity by the γδ T-cell receptor, and third, they have CAR-mediated anti-tumor activity,” Neelapu said during his presentation.

The trial has enrolled 10 patients with CD20+ aggressive N-cell lymphomas as of May 31, 2022, 8 of which are evaluable: 7 with large B-cell lymphoma (LBCL) and 1 with mantle cell lymphoma (MCL). Patients had a median age of 62 years (range, 45-75) and 5 were male. Most patients were heavily pre-treated and had poor prognostic factors and relatively high tumor burdens. Patients had a median of 4 prior lines of therapy (range, 2-5) and 63% (n = 5) were refractory to the last course of systemic therapy. Median IPI score was 4 (range, 2-5). Three patients with diffuse LBCL (38%) had progressed after prior anti-CD19 therapy, including axicabtagene ciloleucel and lisocabtagene maraleucel.

CD20-Targeted CAR T-Cell Therapy Shows Safety, Good Response Rates in B-Cell Non-Hodgkin Lymphoma

All patients received fludarabine and cyclophosphamide conditioning therapy, whether standard lymphodepletion (sLD) or enhanced lymphodepletion (eLD), which had comparable results. Patients then received 1 of 3 ADI-001 dose levels: 3E7 (DL1; n = 3), 1E8 (DL2; n = 3), or 3E8 cells (DL3; n = 2). Participants overall had an overall response rate (ORR) of 75% and a complete response (CR) rate of 75%. DL2 and DL3 together had an ORR of 80% and a CR rate of 80%. The ORR and CR rates were 100% in 3 patients previously treated with CAR T-cell therapy. Stratified, ORR and CR rates were 67% in DL1 (n = 2), 67% in DL2 (n = 2), and 100% in DL3 (n = 2).

There were no cases of grade 3 or higher cytokine release syndrome (CRS) or immune-effector cell-associated neurotoxicity syndrome (ICANS). There was 1 case of grade 1 ICANS in DL2 which resolved within 24 hours without medical intervention, and which was the only treatment-related adverse event (AE) of special interest. There were 2 cases of CRS in DL1, of which occurred in a patient with COVID-pneumonia. This patient also had an AE of infection. There were no dose-limiting toxicities or cases of graft-versus-host disease. No patients discontinued treatment due to AEs.

Cell destination analyses found that γδ cells preferentially home to tissues including lympho nodes, breast, gastrointestinal, and lung tissue. Although progression free survival and overall survival analyses are not yet available, durability seems to be related to dose level and ADI-001 exposure in the blood. Dose escalation is continuing in the study and a fourth dose level (1E9) has been added to the protocol as well as a potential consolidation dosing at DL3 due to the safety profile and evidence of dose-related increase to ADI-001 exposure.

“In this early data, the efficacy appeared to be quite promising in patients who are heavily pretreated with aggressive B-NHL, including those who had prior CD19 CAR T-cell therapy... This early data also suggests promising durability of responses and preliminarily, there appears to be a dose-related increase in durability... This has the potential to have best-in-class clinical efficacy,” Neelapu said.

Neelapu SS, Hamadani M, Miklos DB, et al. A phase 1 study of ADI-001: Anti-CD20 CAR-engineered allogeneic gamma delta (γδ) T cells in adults with B-cell malignancies. Presented at: Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #7509.

100% overall response and complete response rates were seen in patients treated with prior CD19 CAR T-cell therapy. 

Gamma Delta CAR T-Cell Therapy Shows Promising Responses in B-Cell Malignancies 

 TAEST16001 has demonstrated promising clinical activity in advanced soft tissues sarcoma with an acceptable safety profile, according to data from a phase 1 study (NCT04318964).

2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, held both virtually and in Chicago, Illinois

 by Xing Zhang, MD, professor and chief physician, department of Immunotherapy and Medical Oncology of Melanoma and Sarcoma, Sun Yat-sen University Cancer Center.

“The molecular target of the TCR therapy is NY-ESO-01, a cancer testis antigen. TAEST16001 is a TCR-affinity enhanced specific T-cell therapy and expresses an engineered high affinity NY-ESO-01 TCR,” Zhang said during her presentation.

Apheresed T cells were transduced with a lentiviral vector containing NY-ESO-1 TCR and expanded in vitro. Patients received cyclophosphamide (15 mg/kg/day for 3 days) and fludarabine (20 mg/m2/day for 3 days lymphodepleting chemotherapy before TAEST16001 cell infusion. TAEST16001 cells were administered at 4 dose levels (DLs): 5 × 108± 30%, 2 × 109± 30%, 5 × 109± 30%, and 1.2 × 1010± 30%, and patients received interleukin-2 subcutaneous injection for 14 days after infusion.

NK Cell Therapy Avelumab Combo Well Tolerated With Some Clinical Activity in Sarcoma

Twelve patients with advanced soft tissue sarcoma have been enrolled, 3 each in the 4 cohorts, as of December 31, 2021. Seven participants were male and median age was 37.9 years. Participants had a median of 2 prior treatment regimens (range, 1-3).

Overall, 5 patients had a partial response (PR), 5 had stable disease (SD), and 2 had progressive disease (PD) for an overall response rate (ORR) of 41.7%. By cohort, DL1 and DL4 had a 66.7% ORR, DL2 had a 33.3% ORR, and DL3 had a 0% ORR, with 2 PDs and 1 SD. Median time to response was 1.9 months (range, 0.9 to 3.0), and median duration of response was 14.1 months (range, 5.0 to 14.2). Median progression free survival was 7.2 months (95% CI, 2.6-11.7).

TAEST16001 was well-tolerated with no dose-limiting toxicities observed. Grade 3 adverse events (AEs) included lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), and fever (n = 1). Two cases of grade 2 cytokine release syndrome resolved after symptomatic treatment. Investigators did not observe any neurotoxicity or serious AEs related to treatment and maximum tolerated dose (MTD) was not reached. Pharmacokinetic modeling revealed peak expansion of TAEST16001 cells was 6.23 days after infusion, and there was no relationship between clinical response and Cmax/AUC0-28.

“TAEST16001 cells showed an acceptable safety profile, and MTD was not reached. A single TAEST16001 cell infusion resulted in durable tumor responses in a subset of patients with soft tissue sarcoma, encouraging PFS, ORR, and duration of response. A phase 2 study is encouraged due to emerging efficacy data in the phase 1 trial,” Zhang concluded.

Zhang X, Weng D, Pan Q, et al. Phase I clinical trial to assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of NY-ESO-1–specific TCR T-cells (TAEST16001) in HLA-A*02:01 patients with advanced soft tissue sarcoma. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #11502.

Overall response rate was 41.7% and median progression free survival was 7.2 months. 

NY-ESO-1 TCR T-Cell Therapy Shows Clinical Activity in Soft Tissue Sarcoma

“For patients with relapsed refractory diffuse large B cell lymphoma, one of the big unmet needs is what to do for patients who are frail...The ability for us to deliver a therapy such as CAR T-cell in a patient population that historically has been considered as potentially not eligible for transplant would be a very important unmet need for us to define with this clinical trial.”

Axicabtagene ciloleucel (axi-cel; Yescarta; Kite) has demonstrated superiority to standard-of-care (SOC) chemotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) over the age of 65 years, according to new data from the ZUMA-7 study (NCT03391466).

 by Jason Westin, MD, FACP, leader, DLBCL research team, MD Anderson Cancer Center.

ZUMA-7 has enrolled 109 elderly patients as of March 18, 2021, 51 to the axi-cel arm and 58 to the SOC arm. Participants in the axi-cel arm had a median age of 70 years (range, 65-80) and participants in the SOC arm had a median age of 69 years (range, 65-81). The axi-cel arm had more participants with high-risk features, including second-line adjusted International Prognostic Index scores of 2-3 in 53% of participants and elevated lactate dehydrogenase in 61% of participants, compared with 31% and 41% in the SOC arm, respectively.

Westin and colleagues found that the axi-cel arm had superior event-free survival compared to the SOC arm (hazard rate, 0.276; 

<.0001) and higher complete response rates (75% vs 33%). Quality of life analyses from 46 patients in the axi-cel arm and 42 in the SOC arm also revealed statistically significant and clinically meaningful score differences with axi-cel treatment. Score changes from baseline to day 100 after treatment were significantly better in the axi-cel arm for EORTC global health (

<.0001) and physical functioning domains (

= .0019), as well as the EQ-5D-5L visual analogue scale (

<.0001). Scores continued to favor the axi-cel arm over SOC at day 150 (

Axi-cel had a managable safety profile in study participants, although most experienced at least grade 3 treatment-emergent adverse events (AEs; 94%). Similarly, most patients receiving SOC chemotherapy also experienced these AEs (82%). A grade 5 treatment-related AE occurred in 1 patient in the SOC arm and none in the axi-cel arm.

spoke with Westin to learn more about the ZUMA-7 trial and the unmet needs of elderly patients with DLBCL. He also discussed the importance of enrolling diverse patient populations in clinical trials.

Westin J, Locke F, Dickinson M, et al. Clinical and patient (pt)-reported outcomes (PROs) in a phase 3, randomized, open-label study evaluating axicabtageneciloleucel (axi-cel) versus standard-of-care (SOC) therapy in elderly pts with relapsed/refractory (R/R) large B-cell lymphoma (LBCL; ZUMA-7).

Jason Westin, MD, FACP, leader, DLBCL research team, MD Anderson Cancer Center, discussed results from the ZUMA-7 trial at ASCO 2022. 

Axi-Cel Superior to SOC in Elderly Patients with Diffuse Large B-Cell Lymphoma 

CART-ddBCMA, an autologous anti-BCMA chimeric antigen receptor (CAR) T-cell therapy using the novel, synthetic binding D-Domain, has demonstrated clinical activity in 

, according to new data from a phase 1 study (NCT04155749).

by Matthew J. Frigault, MD, instructor, medicine, Harvard Medical School, and clinical director, cellular immunotherapy program, BMT & cellular therapy, Massachusetts General Hospital.

“CART-ddBCMA contains a novel D domain that was computationally designed. It’s comprised of 3 alpha helices that you can mutate the binding surface to get different degrees and characteristics of affinity as well as immunogenicity... Importantly, D domains are actually significantly smaller than traditional T-cell receptor (TCR)-based therapies, single chain-based therapies, or camelid-based therapies... They’re extremely stable at high temperatures and rapidly fold,” Frigault said during his presentation.

The multi-center, open-label study has treated 25 patients with a median age of 66 years (range, 44-76) with 100x10

 CART-ddBCMA cells (cohort 1) and 6 patients with a median age of 60 years (range, 52-65) with 300x10

 cells (cohort 2). Patients in cohort 1 had a median of 5 prior lines of therapy (range, 3-16) and 9 (36%) had extramedullary disease (EMD). Patients in cohort 2 had a median of 4 prior lines of therapy (range, 3-16) and 3 (50%) had EMD. Prior to dosing, patients received fludarabine and cyclophosphamide (30/300 mg/m

Cilta-Cel Yields 100% ORR in Patients With Early Relapse of Multiple Myeloma

Patients were followed up for a median of 9.8 months (range, 2-23.7). Of 16 patients with a minimum follow-up of 12 months and median follow-up of 17.7 months, ORR was 100% and complete response (CR) rate was 81% (n = 13). Eleven patients (69%) continue to have an ongoing response. In 24 patients followed up for at least 6 months, median follow-up was 13.3 months, ORR was 100%, CR rate was 79%, and 22 patients (92%) have an ongoing response. In all 31 patients followed up for at least 1 month, median follow-up was 12.1 months, ORR was 100% and CR rate was 71%.

Overall, very good partial response (VGPR) rate was 88%. Seventeen of 20 (85%) evaluable patients have achieved best minimal residual disease response of ≥10-5. Median duration of response, progression free survival and overall survival are not yet evaluable.

CART-ddBCMA was well-tolerated, with standard cases of neutropenia, anemia, thrombocytopenia, and lymphocytopenia. All patients experienced ctokine release syndrome (CRS) but only 1 case at dose level 2 was grade 3. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 4 patients, 2 at grade 2 or lower and 2 at grade 3 (1 in each dose level). CRS and ICANS resolved within 30 days without sequelae with standard management.

“We examined 2 dose levels and did not reach our maximum tolerated dose. We had high T cell viability and low interpatient variability in our cell manufacturing process. Overall, the AE profile was very positive. We didn’t see any tissue targeted toxicities observed... We had no cases of grade 3 or higher CRS in our dose level 1. We’re excited to begin enrolling the pivotal phase 2 hopefully by the end of this year,” Frigault said.

REFERENCE
Frigault MJ, Rosenblatt J, Cook D, et al. Phase 1 study of CART-ddBCMA in relapsed or refractory multiple myeloma. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract # 8003.

69% of patients followed up for at least 1 year continue to have an ongoing response. 

Synthetic Binding Domain CAR T Therapy Yields 100% ORR in R/R Multiple Myeloma 

B7H3-targeting chimeric antigen receptor T (CAR-T) cells elicit anti-tumor activity and are safe for children and young adults (CYA) with relapsed/refractory solid tumors (R/RST), according to results of the phase 1 STRIVE-02 trial (NCT04483778) presented as a poster at the 

2022 American Society of Clinical Oncology (ASCO) annual meeting

Investigators sought to evaluate the safety and feasibility of genetically modifying a patient’s own T-cells to express scFV-IgG4hinge-CD28tm-4-1BB-zeta B7H3-specific CAR with the methotrexate resistance/selection cassette DHFRdm and the tracking/suicide construct EGFRt. In order to test out the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T-cells would promote the expansion and persistence of the CAR-T cells, the research team launched 2 study arms: Arm A participants received B7H3-specific CAR T cells only, while Arm B participants received CAR T cells directed at B7H3 and CD19, a marker on the surface of B lymphocytes. Arm A data were presented in the ASCO 2022 poster.

The open-label, non-randomized study enrolled 16 CYA (age 11-24, median 17 years) with relapsed or refractory non-central nervous system solid tumors. Three participants received dose level (DL) 1 comprising 0.5 x 10

 CAR-T/kg and 6 received DL 2 comprising 1 x 10

 CAR-T cells/kg. All participants underwent lymphodepletion with fludarabine and cyclophosphamide prior to the CAR-T infusion.

In addition to safety, investigators also tracked maximal tolerated dose and biologically effective dose (BED) by observing toxicity through Day 28 and employing a statistical 3+3 design.

After the first infusion, maximum circulating CAR-T expansion was 4.98 cells/uL (range 0.23-4.98 cells/uL) with median persistence of 28 days (range 14-90). Three of the 9 patients who received the infusion demonstrated best overall response of Stable Disease, and investigators determined DL2 to be the BED.

Investigators observed no dose-limiting toxicities after the first infusion, and the most common side effects, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) dictionary, were fatigue and cytokine release syndrome (CRS) (n = 2, maximum CTCAE grade 2).

One subject who received a second DL2 infusion that resulted in boosted CAR-T expansion of 1590 cells/uL (86% of circulating CD3 cells). The subject experienced CTCAE grade 2 CRS and dose-limiting CTCAE grade 4 liver enzyme elevation that was described as “transient.” The research team observed a partial metabolic response on FDG-PET by PERCIST criteria at Day 28.

“B7H3 CAR T cells are safe and demonstrate anti-tumor activity in CYA with R/RST,” investigators concluded. “CAR-T cell expansion and persistence may be necessary to achieve objective responses. STRIvE-02 Arm B will explore dual expression of CD19 CAR with B7H3 CAR, using lymphocytic CD19 expression to drive CAR expansion and persistence.”

Pinto N, Albert CM, Taylor M, et al. STRIVE-02: a first-in-human phase 1 trial of systemic b7h3 car t cells for children and young adults with relapsed/refractory solid tumors. Poster presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Accessed June 6, 2022.

https://meetings.asco.org/2022-asco-annual-meeting/14400?presentation=206941#206941

Three of the 9 patients who received the infusion demonstrated best overall response of Stable Disease, and investigators determined dose level 2 to be the biologically effective dose. 

STRIVE-02: First-in-Human B7H3 CAR T-Cells for Pediatric Patients With Relapsed/Refractory Solid Tumors

"Cilta-cel has now shown efficacy in early relapse and end stage patients... Because of the high efficacy of cilta-cel in high-risk populations and end stage myeloma, cilta-cel is not only moving to 1 to 3 prior lines, but there are also now several studies that will soon start enrolling patients in the first line. We hope to see that cilta-cel is really superior to autologous stem cell transplant and will improve the clinical outcomes of newly diagnosed myeloma patients.”

Ciltacabtagene autoleucel (cilta-cel; Carvykti; Janssen) yielded deep and durable responses, including a 100% overall response rate (ORR), in patients with multiple myeloma (MM) and early relapse after initial therapy, according to data from cohort B of the phase 2 CARTITUDE-2 study (NCT04133636).

 by Niels van de Donk, MD, PhD, professor, cancer immunology and hematology, Amsterdam University Medical Centers.

Cohort B of CARTITUDE-2 has infused 19 patients, mostly male (74%) with a median age of 58.0 years (range, 44-67), as of January 2022. Patients had a median follow-up of 13.4 months (range, 5.2-21.7) and 79% had received prior autologous stem cell transplant.

Investigators found that ORR was 100.0%, complete response rate was 90%, very good partial response rate was 95%, and 12-month progression free survival rate was 90%. The median time to first response was 0.95 months (range, 0.9–9.7) and median time to best response was 5.1 months (range, 0.9-11.8). Almost all minimal residual disease-evaluable patients (n = 14/15; 93%) achieved MRD 10-5 negativity. Median duration of response was not reached and 12-month event-free rate was 88.9%.

Exploring New Paths for CAR T-Cell Therapy Research in Multiple Myeloma

Cilta-cel had a predictable and manageable safety profile. Grade 3/4 adverse events (AEs) included neutropenia (n = 17), anemia (n = 9), thrombocytopenia (n = 5), lymphopenia (n = 6), and leukopenia (n = 5). Most patients (84%) experienced cytokine release syndrome. Most cases were mild, excepting 1 grade 3/4 case, and all cases resolved. The median time to onset of CRS was 8 days (range, 5–11).

One grade 1 case of immune effector cell-associated neurotoxicity syndrome did occur as well as 1 case of a grade 3 movement and neurocognitive treatment-emergent AE with symptoms of parkinsonism. One death occurred due to progressive disease at day 158 after cilta-cel infusion. Pharmocokinetic analyses revealed that peak CAR-T cellexpansion occurred on day 13.1 (range, 8.96–209.9) and median persistence was 76.9 days (range, 40.99–221.8).

spoke with van de Donk to learn more about the unmet needs in this cohort population and the new findings from the study. He discussed ongoing and future research with cilta-cel, including bringing the therapy up to early lines of treatment.

van de Donk NWCJ, Agha ME, Cohen AD, et al. Biological correlative analyses and updated clinical data of ciltacabtageneautoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2, cohort B. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Poster #453.

Niels van de Donk, MD, PhD, professor, Amsterdam University Medical Centers, discussed positive findings from cohort B of the CARTITUDE-2 study. 

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