ASCO 2022 Highlights: Clinical Updates on Key Oncology Therapies Including J&J’s Carvykti and Novartis’ Scemblix

Text by Li Tom and Osher

The annual American Society of Clinical Oncology (ASCO) meeting is about to begin. This ASCO 2022 will be held in Chicago from June 3 to 7, 2022, in both online and offline formats.

The ASCO Annual Meeting is a prestigious academic exchange event in the global oncology field, showcasing the latest international advancements in clinical oncology research and cancer treatment technologies.

Major pharmaceutical companies will announce the latest advances in cancer research at the annual meeting, partially organized as follows:

01Johnson & Johnson, Legend Biotech Announce Positive Data for Carvykti in Early Myeloma

Latest trial results show that Carvykti, the CAR-T therapy developed by Legend Biotech and its partner Johnson & Johnson, has demonstrated sustained efficacy in patients with multiple myeloma. Early treatment with Carvykti in patients with other conditions has also successfully reduced tumor size. Among heavily pretreated patients who received a single infusion of Carvykti, 54.9% did not experience disease progression, and approximately 70% remained alive.

Moreover, Johnson & Johnson and Legend will also present efficacy data of Carvykti at the annual meeting for patients who relapsed quickly after initial treatment. Among the patients who had received one prior treatment and experienced progression within 12 months, all 19 patients treated with Carvykti showed tumor reduction, with 90% achieving complete response or better.

According to cohort data from Group B of the Phase 2 CARTITUDE-2 trial after a median follow-up of 13.4 months, with patients completing a median follow-up of 4.7 months, the overall response rate reached 88.9%, with 27.8% of patients achieving a complete response or stringent complete response. According to another set of data from Cohort A (patients whose disease progressed after 1 to 3 prior lines of therapy and were refractory to Revlimid), Carvykti achieved an overall response rate of 95% after a median follow-up of 9.7 months.

Currently, Johnson & Johnson and Legend Biotech are preparing for a larger Phase 3 trial, Cartitude-4, to further test the efficacy response in Cohort A. The goal of the trial is to potentially gain second-line treatment approval for Carvykti. However, the two companies have not announced plans for a Phase 3 trial targeting Cohort B. Additionally, Johnson & Johnson has initiated the Phase 3 Cartitude-5 study of Carvykti therapy for newly diagnosed myeloma patients who are ineligible for stem cell transplantation.

02Seagen, Takeda's Adcetris Expected to Become New Lymphoma Combination Drug

Latest data show that in the Phase 3 Echelon-1 study of untreated Stage III/IV Hodgkin lymphoma patients, Adcetris combination therapy demonstrated superiority over the standard ABVD regimen in the secondary endpoint (overall survival). After a median follow-up of six years, patients treated with Adcetris had a 41% reduction in the risk of death compared to those on the standard therapy. In a trial involving 1,334 patients, there were 39 deaths in the Adcetris group versus 64 in the ABVD group. Additionally, the safety profile of the Adcetris combination was consistent with previous studies.

Previously, Adcetris had already received approval for first-line treatment of Hodgkin's disease, but Takeda is still exploring the expansion of the drug's indications. In a submission to ASCO, Seagen included trial data evaluating Adcetris in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The triple combination therapy showed promising efficacy in Phase 1 trials, with 57% of participants experiencing tumor shrinkage. The median progression-free survival time for patients reached 10.2 months, and the overall survival was 14.3 months.

03Thanks to New Leukemia Data, Novartis Optimistically Forecasts Future Sales of Scemblix

Latest data show that in the phase 3 Ascembl trial, 37.6% of chronic myeloid leukemia (CML) patients treated with Scemblix achieved a major molecular response at 96 weeks of treatment. These patients had previously tried at least two prior treatments. The major molecular response rate of Scemblix is also significantly higher than the 15.8% for Pfizer's Bosulif.

Jeff Legos, Global Head of Oncology and Hematology Development at Novartis, explained that achieving a major molecular response with Scemblix means the BCR-ABL protein is no longer detectable in patients' blood. He emphasized that the BCR-ABL protein marker is highly correlated with long-term clinical benefits. In the latest data update, there was a clear difference in the major molecular response rates between Scemblix and Bosulif. At 24 weeks of follow-up, the molecular response rate in the Scemblix group reached 25%, compared to 13% in the Bosulif group.

In terms of safety, after 96 weeks of follow-up, 7.7% of patients in the Scemblix group discontinued treatment due to side effects, compared to 26.3% of those taking Bosulif. Notably, Novartis launched Scemblix because its earlier-market drug Tasigna, which followed Gleevec, will lose patent protection in 2023. Last year, as Gleevec sales dropped by 14% to $1.02 billion, Tasigna’s revenue increased by 5% to $2.06 billion.

In the first quarter of this year, Scemblix achieved sales of $25 million. Vas Narasimhan, CEO of Novartis, stated during the company’s first-quarter earnings call that Scemblix has already captured 20% market share in CML and successfully secured 49% of the total patient share in third-line and other treatments.

04Zanidatamab Demonstrates Antitumor Activity in HER2-Positive Breast Cancer and Gastric Esophageal Cancer

Among 33 evaluable patients with advanced HER2-positive gastric/gastroesophageal junction adenocarcinoma, treatment with zanidatamab and tislelizumab in combination with CAPOX chemotherapy resulted in a confirmed objective response rate (cORR) of 75.8% (25/33), a disease control rate (DCR) of 100% (33/33), and a duration of response (DOR) ranging from 2.1+ to 18.2+ months.

In addition, the latest data also show that the combination of zanidatamab and tislelizumab with CAPOX chemotherapy is well tolerated, with the severity of most treatment-related adverse events (TRAEs) considered mild to moderate (Grade 1 or 2). The most common ≥Grade 3 TRAE was diarrhea, but this side effect is generally well controlled in an outpatient setting.

The release of this latest dataset will also further support Zymeworks’ upcoming global Phase 3 study HERIZON-GEA-01 and NCT05152147, which is evaluating zanidatamab in combination with tislelizumab plus chemotherapy as a first-line treatment for locally advanced, unresectable, or metastatic HER2-positive gastric or gastroesophageal adenocarcinoma. Zymeworks, in collaboration with BeiGene, plans to enroll 714 patients across approximately 300 sites in 38 countries, with patient recruitment expected to conclude by the end of 2023.

05NovalGen Announces First Phase 1/2 Study Data of NVG-111

NovalGen Recently Announced the First Phase 1/2 Study Data of NVG-111, a Novel Bispecific ROR1 Antibody T-cell Engager for Patients with Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL). Early Data Show that the Therapy Has Predictable and Manageable Safety, with Promising Efficacy Prospects.

As of January 31, 2022, six patients had been enrolled in the study, with three patients in the accelerated dose (ADT) cohort and the remaining patients assigned to the fixed dose cohort of 30 µg/day. In the second cohort, early signs of efficacy and evidence of therapeutic response were observed in all patients. Among them, MRD was undetectable in the blood of two patients, one patient showed negative bone marrow MRD, and the remaining patients achieved partial responses.

In the trial, NVG-111 treatment was well-tolerated, with the most common adverse events being transient grade 1 drowsiness, headache, nausea, vomiting, and thrombocytopenia. Dose escalation is still ongoing, including exploration of appropriate dose escalation.

06Ascentage Pharma Announces Seven Clinical Advancements

On May 27, Ascentage Pharma-B announced that the abstracts of seven clinical studies selected for the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting were published on the ASCO official website. These seven studies involve five self-developed products: the third-generation tyrosine kinase inhibitor (TKI) Olverembatinib (HQP1351), Bcl-2 inhibitor APG-2575, MDM2-p53 inhibitor APG-115, ALK inhibitor APG-2449, and Bcl-2/Bcl-xL inhibitor APG-1252.

07BeiGene to Present Eight Research Data Reports from its Solid Tumor and Hematological Malignancy Drug Portfolio

BeiGene's showcased data this time focuses on the latest clinical data of the BTK inhibitor BRUKINSA® (zanubrutinib):

Long-term Safety and Efficacy Results of the Phase 3 ASPEN Trial Comparing BRUKINSA® to Ibrutinib in Patients with Waldenström's Macroglobulinemia, with a Median Follow-up of 43 Months.

Primary Analysis Results of the Phase 2 ROSEWOOD Clinical Trial: BRUKINSA® (Zanubrutinib) in Combination with Obinutuzumab versus Obinutuzumab Monotherapy for Patients with Relapsed/Refractory Follicular Lymphoma.

In addition to announcing the latest clinical trial results of Brukinsa®, BeiGene will also present a poster at the June 5 abstract update session on its early-stage development pipeline and the results of the Phase 3 clinical trial RATIONALE 309 for Tislelizumab. RATIONALE 309 is a Phase 3 clinical trial evaluating the efficacy of Tislelizumab in combination with chemotherapy compared to placebo plus chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma.

08Adagene to Announce Interim Data of ADG126, a Safety Antibody Against CTLA-4

Adagene to Present Interim Data from Phase Ib/II Clinical Trial of ADG126 in the First Stage of Dose Escalation, Demonstrating Best-in-Class Potential Safety of this Anti-CTLA-4 Monoclonal Antibody (mAb). The abstract is titled "A Phase I Study of an Innovative Masked Anti-CTLA-4 Safe Antibody ADG126, Which Achieves Tumor-Specific Activation in Patients with Advanced Solid Tumors, Potently Depletes Regulatory T Cells, and Exhibits Flexible Ligand Blocking Effects."

Key data are as follows:

In this dose-escalation trial involving 16 patients with advanced metastatic solid tumors, approximately one-third of the patients had received third-line or higher treatment, and about one-third of the patients had experienced disease progression after receiving immunotherapy (IO). For cancer patients who have undergone multiple lines of systemic therapy, ADG126 monotherapy was administered intravenously once every three weeks at a maximum dose of 10mg/kg.

No dose-limiting toxicity or treatment-related serious adverse events (SAE) were observed in the repeat-dose trials across all dose groups, with only grade 1 treatment-related adverse events (TRAE) reported. The most common were fatigue (19%) and pruritus (13%).

Plasma pharmacokinetics (PK) of the drug is approximately linear, with activated ADG126 steadily accumulating during repeated dosing at different dose levels. As the first set of clinical data validating the SAFEbody precision masking technology of safety antibodies, the total half-life of ADG126 increased 1.7-fold. The increase in PK of activated ADG126 in humans indicates that the safety antibody is directionally activated within the tumor microenvironment (TME), steadily accumulates, and prolongs drug exposure in tumor tissues, thereby enhancing its efficacy.

Demonstrates Early Antitumor Activity: Two Patients with Cold Tumors Who Had Undergone Multiple Lines of Treatment, One with Ovarian Cancer and the Other with Uveal Melanoma That Progressed After Combination Therapy with Nivolumab and Ipilimumab, Showed Continuous Reduction of Target Lesions by Over 20% Following Treatment. An Increase in CD8+ T Cells Was Also Observed, Potentially Due to the Steady Accumulation and Effect of Activated ADG126 in the Tumor Microenvironment (TME) After Repeated Low-Dose (1 mg/kg) Administration. In the ovarian cancer patient, the tumor biomarker CA-125, indicative of clinical benefit, decreased by up to 77% after the seventh treatment cycle with ADG126 at a dose of 1 mg/kg.

As of February 15, 2022, five of the 16 patients had stable disease, including those with ovarian cancer and uveal melanoma. In this trial, the dosing has been escalated to 20 mg/kg, and the expansion at the 10 mg/kg dose has also begun.

09Gracell Biotechnologies to Present Updated Clinical Data of BCMA/CD19 Dual-Target CAR-T Therapy GC012F for RRMM

On May 27, Gracell Biotechnologies announced that it would present the latest clinical data from a multicenter, investigator-initiated clinical trial (IIT) of its B-cell maturation antigen (BCMA)/CD19 dual-target CAR-T candidate product GC012F for the treatment of relapsed/refractory multiple myeloma (RRMM) in an oral report at the American Society of Clinical Oncology 2022 Annual Meeting (ASCO 2022).

GC012F is a dual-target autologous CAR-T therapy that treats by simultaneously targeting BCMA and CD19. This candidate product is based on the company's proprietary FasTCAR platform technology, which has the advantage of "production completed in one day." In November 2021, GC012F was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma. Several IIT studies are currently being conducted in China to evaluate its efficacy in treating multiple myeloma (MM) and B-cell non-Hodgkin lymphoma (B-NHL).

From October 2019 to November 2021, a total of 28 patients with heavily pretreated RRMM were enrolled in this single-arm, open-label, multi-center IIT study. Patients received a single infusion of GC012F at one of three dose levels: 1x105 cells/kg (DL1), 2x105 cells/kg (DL2), and 3x105 cells/kg (DL3). Among them, 9 patients were newly enrolled after updated data was presented at the 2021 ASCO and EHA Annual Meetings. According to mSMART 3.0 criteria, 89.3% (25/28) of the patients were defined as high-risk. The median number of prior treatment lines for all patients was 5.

As of the data cutoff date of January 26, 2022, 28 patients were evaluated for efficacy, with a median follow-up time of 6.3 months (range: 1.8 - 29.9 months); currently, the study is still conducting ongoing follow-ups with patients to evaluate the depth of response. The objective response rates at different dose levels were as follows: DL1: 100% (2/2), DL2: 80% (8/10), and DL3: 93.8% (15/16). Among all patients evaluable for minimal residual disease (MRD) efficacy, 100% (27/27) achieved MRD negativity; 75% (21/28) of the patients reached minimal residual disease-negative stringent complete response (MRD- sCR).

GC012F demonstrated a safety profile consistent with previous observations, primarily characterized by low-grade cytokine release syndrome (CRS) (Grade 0-2: 93%), with no occurrence of Grade 4 or 5 CRS. No immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was observed. The study will continue to monitor and evaluate the efficacy and safety of GC012F in treating patients, including the best overall response rate (BOR) and duration of response (DoR).

10Youhe Pharmaceutical to Announce Latest Clinical Research Data on CD40 Antibody and CTLA-4 Antibody

On May 27, Eucure Biopharma, a wholly-owned subsidiary of Biocytogen, will present the latest Phase I clinical trial data from Australia for its self-developed YH003 (CD40 antibody, abstract number 2603) and YH001 (CTLA-4 antibody, abstract number 2602) in poster format at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. The studies demonstrate that both YH003 and YH001 exhibit a high tolerated dose and preliminary anti-tumor activity when used in combination with a PD-1 antibody.

Reference Source:

1、ASCO: J&J, Legend reveal more CAR-T data and a look at Carvykti for earlier myeloma in a difficult population

2、ASCO: Seagen, Takeda think Adcetris can become a force as a lymphoma combo drug

3、ASCO: Novartis eyes full nod for Gleevec follow-on Scemblix thanks to new leukemia data

4、Clinical Data Demonstrating Promising Antitumor Activity with Zanidatamab in 1L Setting of HER2‑Positive Breast and Gastroesophageal Cancers to be Presented at ASCO 2022

5、NovalGen announces compelling data from the Phase 1/2 Study of NVG-111 at the ASCO Annual Meeting

6. Official WeChat accounts of major pharmaceutical companies, corporate announcements, etc.