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

The ASCO Annual Meeting is a prestigious academic exchange event in the global oncology field, showcasing the latest cutting-edge clinical oncology research achievements and cancer treatment technologies internationally.

Major pharmaceutical companies will announce the latest advances in cancer research at the annual meeting. Some of the updates are organized as follows:

01

Johnson & Johnson, Legend Announce Positive Early Data for Carvykti in Multiple 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 in patients with rapid relapse after initial treatment at the annual meeting. 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 Cartitutde-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. Based on another set of cohort data from Group A (patients whose disease progressed after 1 to 3 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 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 Group B. Additionally, Johnson & Johnson has also initiated the Phase 3 Cartitude-5 study of Carvykti therapy for newly diagnosed myeloma patients who are ineligible for stem cell transplantation.

02

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

Latest data show that in the phase III Echelon-1 study of untreated stage III/IV Hodgkin lymphoma patients, Adcetris combination therapy outperformed 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 therapy was consistent with previous studies.

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

03

Thanks to New Leukemia Data, Novartis Is Optimistic About Future Sales of Scemblix

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

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, the difference in major molecular response rates between Scemblix and Bosulif was significant. 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 Bosulif users. 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 Q1 earnings call that Scemblix has captured 20% of the market share in CML and successfully secured 49% of the total patient share in third-line and other treatments.

04

Zanidatamab 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 the CAPOX chemotherapy regimen 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 majority of treatment-related adverse events (TRAEs) being mild to moderate in severity (Grade 1 or 2). The most common ≥Grade 3 TRAE was diarrhea, but this side effect can generally be well managed on an outpatient basis.

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

05

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

NovalGen Recently Announced the First Phase 1/2 Study Data of NVG-111, a Novel ROR1 Bispecific Antibody T-cell Engager for 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.

As of January 31, 2022, six patients had been enrolled in the study, with three patients assigned to the accelerated dose (ADT) cohort and the remaining patients allocated 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 other 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 trials are still ongoing, with research projects including exploring appropriate dose escalation levels.

06

Ascentage 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 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.

07

BeiGene to Present Eight Research Data Reports from its Solid Tumor and Hematologic Malignancy Portfolio

The key data showcased by BeiGene this time include the latest clinical data for 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 on its early development pipeline and the results of the Phase 3 clinical trial RATIONALE 309 for Tislelizumab at the Abstract Update Session on June 5. 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.

08

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

Adagene to Present Interim Phase 1b/2 Dose Escalation Data of ADG126, Demonstrating Best-in-Class Potential for Safety of this Anti-CTLA-4 Monoclonal Antibody (mAb). The abstract is titled "A Phase I Study of ADG126: A Novel Masked Anti-CTLA-4 SAFEbody® with Tumor-Specific Activation in Patients with Advanced Solid Tumors, Potent Depletion of Regulatory T Cells and Flexible Ligand Blockade".

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 repeated-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, the total half-life of ADG126 increased 1.7-fold. The increase in PK of activated ADG126 in humans indicates that the safe antibody is directionally activated in the tumor microenvironment (TME), steadily accumulates, and prolongs drug exposure in tumor tissues, thereby enhancing its effect.

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 Nivolumab and Ipilimumab Combination Therapy, 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 Subsequent Activity of Activated ADG126 in the 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 conditions, including those with ovarian cancer and uveal melanoma. In this trial, the dosing was escalated to 20 mg/kg, and the expansion at the 10 mg/kg dose had also begun.

09

Gracell Biotechnologies to Present Updated Clinical Data on 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, offering 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, this single-arm, open-label, multi-center IIT study enrolled a total of 28 RRMM patients who had received extensive prior treatment. The enrolled patients received a single infusion of GC012F at three dose levels: 1x105 cells/kg body weight (DL1), 2x105 cells/kg body weight (DL2), and 3x105 cells/kg body weight (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 cut-off 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 assess 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 patients reached minimal residual disease-negative stringent complete response (MRD- sCR).

The safety profile of GC012F was consistent with previous observations, primarily manifesting as 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 (BOR) and duration of response (DoR).

10

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

On May 27, YuceBio, 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 #2603) and YH001 (CTLA-4 antibody, Abstract #2602) in poster format at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. The studies show that both YH003 and YH001 demonstrate high tolerable doses and preliminary anti-tumor activity when combined 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.

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