2021 ASCO | A quick overview of the major research progress of the immunization session

The 2021 American Society of Clinical Oncology (ASCO) annual meeting will be held online from June 4th to 8th.
As one of the largest and most popular events in oncology, the ASCO annual meeting will showcase the latest cutting-edge developments to scholars from all walks of life.

At present, most of the abstracts have been published on the official website.
What are the important research developments in the immunotherapy special session that has attracted much attention? Come and watch.

HPV 16-positive malignant tumors A phase II study (Abstr 2501) to evaluate the feasibility of the combination of PDS0101, M9241 and bintrafusp alfa in patients with HPV 16-positive malignant tumors (Abstr 2501) There are more than 630,000 cases of HPV-related malignancies each year, including Cervical cancer, oropharyngeal cancer and anal cancer.

Most of them are caused by HPV 16.

About 15-20% of HPV-related malignancies respond to PD-(L)1 inhibitors, but there is no effective treatment standard for the vast majority of patients receiving these immunotherapies.

PDS0101 is a liposomal polypeptide therapeutic vaccine targeting HPV16 E6/E7; M9241 is a tumor-targeted immune cytokine; bintrafusp alfa (M7824) is a bifunctional fusion protein, derived from human transforming growth factor β receptor Ⅱ The extracellular domain (ECD) of (TGFβRⅡ or TGFβTrap) is covalently linked with anti-PD-L1 antibody.

This phase II study evaluated the feasibility of the combination of PDS0101, M9241 and bintrafusp alfa in 16 patients with HPV 16 positive malignancies.

Safety analysis showed that 4 patients (28.
6%) had grade 3 treatment-related adverse events (TRAE), and 1 case had grade 4 TRAE.

Efficacy analysis showed that 10 patients (71%) achieved objective remission (1 complete remission [CR], 9 partial remission [PR]).

Of the 6 patients who had not previously received immune checkpoint inhibitor therapy, 5 (83%) achieved objective remission, and 5 of the 8 patients refractory to immune checkpoint inhibitor (63%) achieved objective remission.

The study showed that the safety of the PDS0101, M9241, and bintrafusp alfa three-drug combination regimen is manageable, and it provides early evidence that it is clinically significant in patients with newly treated immune checkpoint inhibitors and refractory HPV 16-positive advanced malignancies.
active.

The first report of the safety/tolerability and preliminary anti-tumor activity of HB-201 and HB-202 in HPV16-positive cancer patients (Abstr 2502) HB-201 and HB-202 are replicated live attenuated vectors, based on lymphatics, respectively Cellular choroidal meningitis virus and Pichinde virus, which express the same non-oncogenic HPV16 E7E6 fusion protein to induce tumor-specific T cell responses.

This phase I/II study mainly evaluates the safety/tolerability and preliminary anti-tumor activity of HB-201 monotherapy and HB-201&HB-202 alternative therapy in 25 HPV16-positive cancer patients.

Safety analysis showed that: no dose-limiting toxicity was observed.

Treatment emergency adverse events (TEAE) occurred in 21 patients (84%), including fatigue, fever, nausea, loss of appetite, anemia, joint pain, chills, constipation, diarrhea, hypertension, flu-like, pneumonia, and vomiting.

It was generally mild or moderate, and TRAE occurred in 14 patients (56%).

Six patients (24%) had severe TEAEs, and fatigue was the only grade ≥3 TEAE that was assessed as being related to the study drug.

TEAEs will not cause treatment interruption.

The curative effect of 18 patients can be evaluated.

Among the 16 patients who received HB-201 monotherapy, 2 patients achieved PR (including 1 unrecognized CR patient), and 6 patients were in stable condition (SD).

The 2 patients who received alternate treatment with HB-201 and HB-202 were all SD.

The longest duration of remission (DOR)-4.
8 months (144 days) was observed in patients with head and neck squamous cell carcinoma (HNSCC) treated with HB-201, and the maximum tumor diameter was reduced by 60%.

The study shows that HB-201 monotherapy and HB-201&HB-202 alternative therapy are well tolerated, and HB-201 monotherapy has shown preliminary anti-tumor effects in treated patients with HPV16-positive HNSCC and other solid tumors active.

Solid tumor SHR-1701 (a PD-L1 & TGF-β double antibody) is used in the phase 1 study (Abstr 2503) of patients with advanced solid tumors.
SHR-1701 is an anti-PD-L1 monoclonal antibody developed by Hengrui and TGF- Fusion protein of β Trap.

The team of Professor Lin Shen from Peking University Cancer Hospital carried out this dose-escalation and expansion phase I clinical study to evaluate the safety and preliminary anti-tumor activity of SHR-1701 in refractory solid tumors.

In 17 patients who were partly enrolled in dose-escalation, no dose-limiting toxicity (DLT) was observed, and the maximum tolerated dose (MTD) was not reached.

Another 32 patients were added to the dose expansion part.

Among the 49 enrolled patients, 33 patients (67.
3%) had previously received ≥2 lines of systemic therapy.

Data as of October 30, 2020, the median duration of SHR-1701 exposure was 6.
0 weeks (range 2.
0-78.
6).

The most common TRAEs are elevated ALT/AST, anemia, hypothyroidism, and elevated bilirubin/conjugated bilirubin, with an incidence of >15%.

The researchers reported that the incidence of immune-related side effects (irAEs) was 46.
9%, and 4 patients received systemic glucocorticoid therapy.

Hypothyroidism and skin rashes are the most common irAEs, with an incidence of >10%.

The incidence of ≥3 grade TRAEs was 18.
4%.

The incidence of irAEs ≥ grade 3 was 10.
2%.

One patient died prematurely due to liver failure, which was probably caused by tumor progression.

Pharmacokinetic (PK) analysis showed that SHR-1701 has a linear relationship with dose exposure in the dose range of 1 ~ 30 mg/kg.

Peripheral blood PD-L1 occupancy rate exceeded 90% in all dose groups, and TGF-β1 capture was almost detected in all dose groups.

Of the 49 patients, 45 patients completed at least one efficacy evaluation.

The objective response rate (ORR) was 17.
8% (95% CI, 8.
0%-32.
1%), and 8 patients achieved PR (2 cases of lung adenocarcinoma, 1 case of hepatocellular carcinoma, 1 case of esophageal squamous cell carcinoma, 1 case of dMMR colorectal cancer) Carcinoma, 1 case of renal cancer, 1 case of epiglottic cancer, 1 case of pancreatic acinar cell carcinoma).

The disease control rate (DCR) was 40.
0% (18/45; 95%CI, 25.
7%-55.
7%).

Most PR patients are still responding (7/8), and the median DoR has not yet been reached.

Based on safety, PK, pharmacodynamics (PD) and efficacy data, the investigator recommends 30mg/kg Q3W as the recommended dose (RP2D) for the Phase II clinical study.

COM701±Navulimab is used in a phase I study of patients with advanced solid tumors (Abstr 2504) COM701 is a new humanized IgG4 monoclonal antibody that can be associated with the immunoglobulin domain (PVRIG) of the poliovirus receptor High-affinity binding, thereby preventing its interaction with the ligand PVRL2.

Preclinical data show that COM701 targeting PVRIG can effectively stimulate the anti-tumor immune response of certain cancers, such as breast cancer, endometrial cancer, ovarian cancer and lung cancer, especially in the patient population that is slow to respond to current immune checkpoint inhibitors .

In addition, COM701 and PD-1/TIGIT antibody have a synergistic effect, which can enhance the function of T cells, reduce tumor growth, and improve anti-tumor response.

This phase I study aims to evaluate the safety and tolerability of escalating doses of COM701 monotherapy and the combination with nivolumab in the treatment of advanced solid tumors.

In terms of safety, no DLT was observed.

COM701 single agent group (N = 38) TEAE incidence: no AE (4 cases), ≤2 (21 cases), 3 (11), 4 (1), 5 (1, PD ), the most common AEs are fatigue and nausea; the combined treatment group (N = 16) TEAE incidence: ≤ grade 2 (8 cases), grade 3 (7 cases), grade 5 (1 case, PD), the most common AE is fatigue and elevated AST.

Efficacy analysis showed that 1 patient with platinum-resistant primary peritoneal cancer in the COM701 single-drug group was evaluated as PR, lasting for 14 months.

In the combined treatment group, 1 patient with anal squamous cell carcinoma (SCCA) was confirmed as CR for 18 months; 1 patient with renal cell carcinoma was confirmed as SD for 13 months; 30% (6/20) of mucoepidermoid carcinoma (MEC) The patient is SD.

Among the 16 refractory patients, 9 (56%) had the best response ≥SD; of the 18 patients who had been treated with immune checkpoint inhibitors, 13 (72%) had the best response ≥SD.

The study showed that COM701±nivolumab was well tolerated and showed encouraging anti-tumor activity.

Preliminary clinical and biological results of GB1275±pembrolizumab in advanced solid tumors (Abstr 2505) With the continuous in-depth research on the important role of tumor-associated macrophages (TAM) in regulating the anti-tumor immune response, TAM has been It has become an important target in immunological clinical research, using the plasticity of macrophages to promote the transformation of macrophages to an immunostimulatory phenotype, so as to activate the host's anti-tumor immunogenicity and turn "cold tumors" into "hot tumors.
"
GB1275 is a new type of CD11b regulator that can reduce MDSC and TAM in tumor sites, repolarize M2 immunosuppressive TAM to M1 phenotype, thereby increasing tumor infiltration of activated CD8+ T cells in vivo.

The KEYNOTE A36 study is a phase I/II clinical study that explores GB1275 as a single agent and combined with pembrolizumab in the treatment of specific advanced solid tumors.

The dose escalation is based on the standard 3+3 design, and the phase II basket expansion adopts the Simon two-stage optimization design.

Plan A (GB1275 single agent) and B (GB1275 combined with pembrolizumab) were used in the dose-escalation phase.

In terms of safety, no DLT was reported.
53.
3% (24/45) of the subjects had GB1275-related adverse events.
Photosensitivity (20.
0%), paresthesia (13.
3%) and pruritus (13.
3%) were the most common (≥10) %).

In protocol A, 31.
6% (6/19) of the subjects were confirmed as SD, and in protocol B, the proportion was 56.
3% (9/16).

One patient with MSS colorectal cancer (CRC) who received plan B treatment was confirmed to have PR and was treated for 263 days; one patient with gastric cancer (GC) received SD and was treated for 227 days.
This patient had previously received due to disease progression Pembrolizumab + bavituximab treatment (<3 months).

Both subjects are continuing treatment.

The dose of GB1275 in protocol A and protocol B was gradually increased to 1200 mg, which proved to be well tolerated as a single agent and in combination with pembrolizumab in patients with advanced cancer.

Encouraging anti-tumor activity of protocol B (800 mg) was observed in MSS CRC and GC subjects.

The investigator recommended GB1275 800 mg BID + Pembrolizumab 200 mg IV q3w for extended evaluation.

Preliminary results of a phase II clinical study of APG-115 combined with pembrolizumab in patients with unresectable/metastatic melanoma or advanced solid tumors who have failed immunotherapy (Abstr 2506) APG-115 is an oral, highly selective The small molecule MDM2 inhibitor has a high binding affinity to MDM2, and restores the tumor suppressor activity of p53 by blocking the MDM2-p53 interaction.

This is an open, multi-center phase II clinical study conducted in the United States to evaluate the safety, tolerability, PK, PD and anti-tumor of APG-115 combined with pembrolizumab in patients with advanced solid tumors active.

A total of 84 patients were included in the study.

APG-115 is taken orally once every other day at a dose of 150 mg of RP2D and combined with pembrolizumab.

There are 6 research cohorts in this study, namely: PD-1 / PD-L1 inhibitor-resistant melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma; malignant peripheral nerve tenoswanomas that have failed conventional treatment ( MPNST), liposarcoma and ATM mutant solid tumors.

Efficacy evaluation showed that PD-1 / PD-L1 inhibitor-resistant melanoma cohort (n=26): 1 out of 5 patients with uveal (ocular) melanoma was confirmed as PR; among 5 patients with mucosal melanoma 2 cases achieved PR (1 case confirmed + 1 case not confirmed); 1 of 11 patients with skin melanoma achieved PR (confirmed).

The ORR of the melanoma cohort reached 17.
4% (4/23), and the DCR was 60.
9% (14/23).

MPNST cohort (n=3): 1 case of persistent PR (unconfirmed).

In the PD-1/PD-L1 inhibitor-resistant NSCLC (n=14) and urothelial carcinoma (n=5) cohorts, there was 1 confirmed PR.

In terms of safety, among the observed TRAEs of any grade, those with an incidence greater than 10% have nausea, thrombocytopenia, vomiting, fatigue, decreased appetite, diarrhea, neutropenia, and anemia.

The study showed that APG-115 combined with pembrolizumab is well tolerated, or can restore the anti-tumor effect of patients who are resistant or intolerant to tumor immune drugs.

Safety and effectiveness of new anti-CD20/CD19 bispecific CAR T cell therapy (C-CAR039) for hematological tumors in relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (B-NHL) (Abstr 2507) C-CAR039 is a new type of second-generation 4-1BB bispecific CAR-T that targets CD19 and CD20 antigens and optimizes the bispecific antigen binding domain.

C-CAR039 can eradicate CD19/CD20 single-positive or double-positive tumor cells both in vivo and in vitro.

Tissue cross-reactivity and genome-wide membrane proteome array studies further confirmed the specificity of C-CAR039.

The study is to carry out the GMP preparation of C-CAR039 in a serum-free, fully enclosed semi-automatic system.
The team of Professor Liang Aibin from Tongji Hospital of Tongji University carried out a dose escalation and expansion study to evaluate C-CAR039 in r/r B-NHL patients.
In the safety and efficacy.

C-CAR039 was administered intravenously after 3 days of cyclophosphamide combined with fludarabine pretreatment regimen.

As of January 31, 2021, 28 patients have received infusions, of which 25 (DLBCL[22]; PMBCL[1]; tFL[1]; FL[1]) ranged from 1.
0 x 106 to 5.
0 x 106 CAR- The safety and efficacy can be evaluated within the dose range of T cells/kg.

The median age was 54 years (range 28-71 years), the median number of previous treatment lines was 3 (range 1-5), 76% (19/25) of patients were in Ann Arbor stage III/IV, 80% (20/25) patients were refractory to the last treatment.

Five patients (20%) received bridging therapy.

According to the ASTCT 2019 standard, cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome (ICANS) are graded.

Among the 25 patients, 24 (96%) developed CRS, 23 (92%) were grade 1 or 2 and 1 patient was grade 3.

The median time to occurrence of CRS was 3 days (range 0-10 days), and the median duration was 4 days (range 1-25 days).

Grade 1 ICANS occurred in 2 patients.

88%, 40%, 16%, and 0% of patients reported grade 3 neutropenia, anemia, thrombocytopenia, and infection, respectively.

The efficacy results showed that the best ORR was 92%, the CR rate was 84%, and the median time to remission was 1.
0 months (range 0.
9-1.
2 months).

At a median follow-up of 5.
3 months, 76% maintained CR.

The Kaplan Meyer estimate of PFS at 6 months was 87.
3% (95% CI, 71.
2-100.
0).

The median DOR has not yet been reached.

In addition, C-CAR039 exhibits surprising cell dynamics characteristics.

Among the 25 evaluable patients, the median Tmax was 11 days, the median Cmax was 139,497 copies/mg gDNA, and the median AUC0-28DAY was 1,673,844 days* copies/μg gDNA.

The study showed that C-CAR039 showed good safety characteristics and promising efficacy in patients with r/r B-NHL, which may differentiate it from existing therapies.

Early clinical efficacy signals are encouraging, and are superior to anti-CD19 CAR-T and peer therapies.

The above results will be evaluated in more patients with longer follow-up time to confirm safety, efficacy and duration of remission.

Safety and efficacy of new anti-CD20 CAR-T cell therapy in patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) who failed CD19 CAR-T therapy (Abstr 2508) The recurrence caused by the loss of CD19 antigen target is a therapeutic challenge for CD19 CAR-T therapy.

These patients generally have a poor prognosis and high unmet medical needs.

CD20 is a proven therapeutic target in B-NHL and is supported by approved and widely used monoclonal antibody therapy.

C-CAR066 is a new second-generation CAR-T therapy targeting CD20 antigen.

Preclinical studies have shown that the anti-tumor activity of C-CAR066 is better than scFV derived from Leu16, rituximab and Obinutuzumab, and CAR-T against CD19 BBZ CAR and FMC63.

Professor Liang Aibin’s team conducted this phase I clinical trial to evaluate the safety and efficacy of C-CAR066 in r/r B-NHL subjects who have previously received anti-CD19 CAR-T treatment.

The GMP preparation of C-CAR066 is a serum-free, fully enclosed semi-automatic system.

A 3-day pretreatment regimen of cyclophosphamide combined with fludarabine was used, followed by a single infusion of C-CAR066.

Allow bridging therapy.

As of January 31, 2021, 7 patients (6 cases of diffuse large B-cell lymphoma [DLBCL], 1 case of transforming follicular lymphoma [tFL]) were enrolled and received C-CAR066 infusion, with a dose range It is 2.
0 x 106-4.
8 x 106 CAR-T cells/kg.

The preparation success rate is 100%.

The median age was 51 years (range 41-62 years), and 42.
9% (3/7) of patients were male.

The median number of previous treatment lines was 5 (range, 2-6).

One patient (14.
3%) received autologous stem cell transplantation (ASCT), and one patient received bridging therapy.

CRS and ICANS are classified according to the ASTCT 2019 standard.

CRS occurred in all 7 patients, most (85.
7%) were grade 1 or 2.
One patient developed grade 4 CRS and recovered after tocilizumab and corticosteroid treatment.

The median time to the occurrence of CRS was 5 days (range: 1-9), and the median duration was 4 days (range: 2-17).

ICANS did not occur.

57.
1%, 42.
9%, 28.
6%, and 14.
3% of patients reported grade 3 neutropenia, anemia, thrombocytopenia, and infection, respectively.

With a median follow-up of 7.
8 months, the best ORR was 100%, and 71.
4% (5/7) achieved CR.

The median time to remission was 1.
0 months (range: 0.
9-2.
7 months).

The median time to CR was 2.
7 months (range 0.
9-2.
8 months).

As of the data cutoff date, 3 patients (2 PR and 1 CR) had disease progression.

The median DOR was not reached.

The study showed that C-CAR066 showed good safety and promising efficacy in r/r B-NHL patients who failed CD19 CAR-T treatment.

These results indicate that C-CAR066 has a different mechanism of action compared with anti-CD-19 CAR-T therapy, and can provide a new treatment plan to solve the unmet medical needs of B-NHL patients who have failed anti-CD19 CAR-T therapy.

References: 1.
Phase II evaluation of the triple combination of PDS0101, M9241, and bintrafusp alfa in patients with HPV 16 positive malignancies.
2021 ASCO.
Abstr 2501.
2.
First report of the safety/tolerability and preliminary antitumor activity of HB-201 and HB-202, an arenavirus-based cancer immunotherapy, in patients with HPV16+ cancers.
2021 ASCO.
Abstr 2502.
3.
Phase 1 study of SHR-1701, a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with advanced solid tumors .
2021 ASCO.
Abstr 2503.
4.
COM701 with or without nivolumab: Results of an ongoing phase 1 study of safety, tolerability and preliminary antitumor activity in patients with advanced solid malignancies (NCT03667716).
2021 ASCO.
Abstr 2504.
5.
Preliminary clinical and biologic results of GB1275, a first-in-class oral CD11b modulator, alone and with pembrolizumab,in advanced solid tumors (KEYNOTE A36).
2021 ASCO.
Abstr 2505.
6.
Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (IO) drugs.
2021 ASCO.
Abstr 2506.
7.
Safety and efficacy of a novel anti-CD20/CD19 bi-specific CAR T-cell therapy (C-CAR039) in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).
2021 ASCO.
Abstr 2507.
8.
Safety and efficacy of a novel anti-CD20 chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory ( r/r) B-cell non-Hodgkin lymphoma (B-NHL) patients after failing CD19 CAR-T therapy.
2021 ASCO.
Abstr 2508.
Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (IO ) drugs.
2021 ASCO.
Abstr 2506.
7.
Safety and efficacy of a novel anti-CD20/CD19 bi-specific CAR T-cell therapy (C-CAR039) in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma ( B-NHL).
2021 ASCO.
Abstr 2507.
8.
Safety and efficacy of a novel anti-CD20 chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL ) patients after failing CD19 CAR-T therapy.
2021 ASCO.
Abstr 2508.
Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (IO ) drugs.
2021 ASCO.
Abstr 2506.
7.
Safety and efficacy of a novel anti-CD20/CD19 bi-specific CAR T-cell therapy (C-CAR039) in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma ( B-NHL).
2021 ASCO.
Abstr 2507.
8.
Safety and efficacy of a novel anti-CD20 chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL ) patients after failing CD19 CAR-T therapy.
2021 ASCO.
Abstr 2508.
in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (IO) drugs.
2021 ASCO.
Abstr 2506.
7.
Safety and efficacy of a novel anti-CD20/CD19 bi-specific CAR T-cell therapy (C-CAR039) in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).
2021 ASCO.
Abstr 2507.
8.
Safety and efficacy of a novel anti-CD20 chimeric antigen receptor ( CAR)-T cell therapy in relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) patients after failing CD19 CAR-T therapy.
2021 ASCO.
Abstr 2508.
in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (IO) drugs.
2021 ASCO.
Abstr 2506.
7.
Safety and efficacy of a novel anti-CD20/CD19 bi-specific CAR T-cell therapy (C-CAR039) in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).
2021 ASCO.
Abstr 2507.
8.
Safety and efficacy of a novel anti-CD20 chimeric antigen receptor ( CAR)-T cell therapy in relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) patients after failing CD19 CAR-T therapy.
2021 ASCO.
Abstr 2508.
Abstr 2507.
8.
Safety and efficacy of a novel anti-CD20 chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) patients after failing CD19 CAR-T therapy.
2021 ASCO.
Abstr 2508.
Abstr 2507.
8.
Safety and efficacy of a novel anti-CD20 chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) patients after failing CD19 CAR-T therapy.
2021 ASCO.
Abstr 2508.