ASCO2021 Preview：劝君更尽一杯酒 西出阳关无故人

第一批尽量先把Ph3、Oral和你懂的之类的撸一下，然后再细细挖坟

目前这5个还没online

PARP7 inhibitor RBN-2397 in patients with advanced solid tumors

https://meetinglibrary.asco.org/record/195774/abstract

PARP7抑制可以恢复干扰素信号传导，抑制肿瘤生长并诱导获得性免疫

As of 4 January 2021, 47 pts were treated: 25 pts in the intermittent schedule (25 to 500 mg BID) and 22 patients in the continuous schedule (100 to 400 mg BID).

  • The most frequent RBN-2397-related AEs (all grades) were dysgeusia (26%), decreased appetite (13%), fatigue (11%), and diarrhea (11%).

  • Gr 3/4 RBN-2397-related AEs all occurred in 7 pts (15%) at doses ≥ 200 mg: diarrhea (2 pts, 4%), increased ALT, AST, and bilirubin (1 pt, 2%), and fatigue, anemia, neutropenia, and thrombocytopenia in 1 pt (2%) each.

  • The 2 DLTs were Gr 3 febrile neutropenia (400 mg continuous schedule) and Gr 4 increase in ALT/AST (500 mg intermittent schedule).

Plasma exposures generally increased dose dependently with the majority at or above the projected efficacious range based on animal studies.

All evaluable baseline tumor biopsies showed evidence of PARP7 expression as measured by mRNA in situ hybridization (n = 11; Median tumor H score: 128).

  • In 5 evaluable tumor biopsy pairs, increases in interferon-stimulated gene expression were observed post RBN-2397, consistent with activation of Type I IFN.

  • CXCL10 mRNA increased in all evaluable on-treatment biopsies (1.5 to 8-fold).

  • Several on-treatment biopsies showed enrichment for immune response gene sets that was accompanied by an increase in CD8+ T cells and Granzyme B expression, evidence for induction of an adaptive immune response post RBN-2397.

  • This increase in immune response related genes and CD8+ T cells was observed in a pt with metastatic squamous NSCLC who has been on study for 16+ months.

安全性说的过去，也找到了和免疫激活相关的标志物，但是转导到疗效上就。。。。

1 pt with HR+, HER2- breast cancer achieved a confirmed PR at 100 mg and 8 pts had SD for ≥18 weeks (RECIST 1.1).

TNO-155

https://meetinglibrary.asco.org/record/195783/abstract

单药的结果很早就有预期，但好在安全性还行，可以折腾

Methods:

CTNO155X2101 (NCT03114319) is an ongoing first-in-human, open-label dose escalation/expansion trial of TNO155 in adults with advanced solid tumors. The primary objective is to characterize the safety and tolerability of TNO155 and identify regimen(s) for future study. Secondary assessments included pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy. Here we present data from TNO155 single agent escalation.

Results:

As of 10/26/2020, 118 patients received TNO155 in variable schedules: once (QD; 1.5–70 mg; n = 55) or twice daily (BID; 30–50 mg; n = 25) in a 2 weeks on/1 week off (2w/1w) cycle; or QD in a 3w/1w cycle (30–60 mg; n = 32), or continuously (40 or 50 mg QD; n = 6). The most common cancer diagnoses treated were colorectal (54%), gastrointestinal stromal tumor (16%), non-small cell lung (12%), and head & neck (8%). The median number of prior antineoplastic therapies was 4 (range 1–10).

Overall 109 patients (92%) have discontinued study treatment, 94 (80%) for progressive disease and 6 (5%) for adverse events (AEs).

TNO155 showed rapid absorption (median day 1 Tmax̃1.1 hours), an effective median T½ of ̃34 hours, and near dose-proportional exposure at day 14 (power model: AUCτ beta = 1.09 [90% CI 1.02–1.16]).

AEs were mostly Grade 1/2 and generally consistent with on-target effects of SHP2 inhibition. The most common treatment-related AEs (all grades) were increased blood creatine phosphokinase (n = 33, 28%), peripheral edema (n = 31, 26%), diarrhea (n = 31, 26%), and acneiform dermatitis (n = 27, 23%).

The most common treatment-related Grade ≥3 AEs were decreased platelets (n = 5, 4%), increased aspartate aminotransferase, diarrhea, and decreased neutrophils (each n = 4, 3%).

The best observed response was stable disease (SD) per RECIST 1.1, reported in 24 (20%) patients, with a median duration of SD of 4.9 months (range 1.7–29.3).

Evidence of SHP2 inhibition, as measured by change in DUSP6 expression by qPCR in paired pre- vs. on-treatment tumor samples, was seen in the majority of patients treated with TNO155 doses ≥20 mg/day (≥25% reduction, 38/42 [90%]; ≥50% reduction, 25/42 [60%]). Analysis of tumor whole-transcriptome RNA sequencing data is ongoing.

Conclusions:

TNO155 shows favorable pharmacokinetic properties and promising early safety and tolerability data at doses with evidence of target inhibition. The optimal dose using several schedules is still under evaluation. Studies of TNO155 in combination with other agents, including nazartinib (mutant-selective EGFR inhibitor[i]), adagrasib (KRAS G12Ci), spartalizumab (anti-PD-1 antibody), ribociclib (CDK4/6i), and dabrafenib (BRAFi) with LTT462 (ERKi), are ongoing (NCT03114319, NCT04330664, NCT04000529, NCT04294160).

COM701 with or without nivolumab

https://meetinglibrary.asco.org/record/196091/abstract

单药和联合在后线都很一般，两个还不够，估计还要加上TIGIT了，加上COM701是IgG4，所以一度怀疑前天小贵子引进的双抗的另一个target是PVRIG

Results:

  • No DLTs were reported in Arms A or B.

  • COM701 PK profile similar in Arm A, 20 mg/kg IV Q4 wks (cohort 8) and Arm B cohort 5 (COM701 20 mg/kg + NIVO 480 mg; all IV Q4 wks).

  • Frequency of TEAEs in safety population (N=54 pts): pts on COM701 mono (N=38)- No AE (4), Grade≤2 (21), G3 (11), G4 (1), G5 (1, PD),

  • pts on combo (N=16) - Grade≤2 (8), G3 (7), G5 (1, PD).

  • Serious TEAE: pts on COM701 mono 11/38, pts on combo 6/16.

  • Most frequent AEs in Arm A: Grade ≤2 fatigue 12/38 pts (31%), nausea 9/38 (23%); Arm B: fatigue 7/16 pts (44%) and AST increased 4/16 pts (25%).

Antitumor activity -

  • in Arm A (cohort 8), a pt with platinum resistant primary peritoneal cancer had confirmed PR ongoing 14 months.

  • In Arm B (COM701 10 mg/kg + NIVO 480 mg, all IV Q4 wks), a pt with anal SCCA; confirmed CR, ongoing 18 months, last tx with prior PD on NIVO. In addition, a pt with renal cell CA had confirmed SD [ongoing 13 months, COM701 0.3 mg/kg + NIVO 360mg; IV Q3 wks],]

  • In MEC, 30% (6/20 pts) had best response of SD [1-endometrial, 3 NSCLC, 2 OVCA], 2 pts [NSCLC, OVCA] ongoing at 6/4 months.

  • Overall 16pts had prior tx-refractory disease, 9(56%) had best response of ≥SD. Of 18 pts with prior tx with ICI, 13 (72%) had best response of ≥SD. Datacut 14Dec2020.

RELATIVITY-047：Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in 1L MEL

https://meetinglibrary.asco.org/record/201596/abstract

主要终点 10.1 vs 4.6 m HR  0.75  P = 0.0055，12mo PFSR 47.7% vs 36.0%，所有亚组都能观察到PFS的获益，Gr3-4 TRAE 略高 18.9% vs 9.7%当然远远好于NIVO+IPI，因TRAE引起的治疗终止 14.6% vs 6.7%，治疗相关的死亡分别3例和2例

目测是不属于CTLA4的：CM-067 O+Y vs O vs Y in 1L MEL regardless of BRAF status

  • ORR 58% vs 45% vs 19%

  • PFS 11.5 mo vs 6.9 mo vs 2.9mo【O+Y vs Y HR 0.42，O vs Y HR 0.53】

  • OS NR(>60mo) vs 36.9mo vs 19.9mo【O+Y vs Y HR 0.52，O vs Y HR 0.63】

CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma

http://meetinglibrary.asco.org/record/195983/abstrac

With a minimum follow-up of 6.5 y, median OS was 72.1 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI (table).

Median time from randomization to subsequent systemic therapy was not reached (NR; 95% CI, 59.6–NR) with NIVO + IPI, 25.2 mo (95% CI, 16.0–43.2) with NIVO, and 8.0 mo (95% CI, 6.5–8.7) with IPI; 36%, 49%, and 66% of pts, respectively, received any subsequent systemic therapy.

Median treatment-free interval (which excluded pts who discontinued follow-up prior to initiation of subsequent systemic therapy) was 27.6 mo (range, 0–83.0), 2.3 mo (range, 0.2–81.6), and 1.9 mo (range, 0.1–81.9) with NIVO + IPI, NIVO, and IPI, respectively.

Of the pts alive and in follow-up, 112/138 (81%; NIVO + IPI), 84/114 (74%; NIVO), and 27/63 (43%; IPI) were off treatment and never received subsequent systemic therapy; 7, 8, and 0 pts, respectively, were still on treatment.

Grade 3/4 treatment-related adverse events were reported in 59% of NIVO + IPI-treated pts, 24% of NIVO-treated pts, and 28% of IPI-treated pts. Since the 5-y analysis, no new safety signals were observed and no additional treatment-related deaths occurred.

Final overall survival for the phase III KN177 study 

https://meetinglibrary.asco.org/record/195775/abstract

Median (range) study follow-up was 44.5 mo (36.0-60.3) with pembro vs 44.4 mo (36.2-58.6) with chemo. 56 (36%) pts crossed over from chemo to pembro, with 37 more receiving anti-PD-1/PD-L1 therapies off study (60% effective crossover rate in the ITT).

The HR for OS favored pembro vs chemo with a trend toward reduction in the risk of death (HR 0.74; 95% CI, 0.53-1.03; P=0.0359; median not reached [NR] vs 36.7 mo); this difference did not reach statistical significance. 

Sensitivity analysis by the rank-preserving structure failure time model and inverse probability of censoring weighting showed OS HRs of 0.66 (95% CI 0.42-1.04) and 0.77 (95% CI 0.44-1.38), respectively.

Pembro vs chemo met the prespecified criteria for PFS superiority at IA2. At final analysis, median PFS was 16.5 mo vs 8.2 mo (HR 0.59; 95% CI, 0.45-0.79), but was not formally tested per analysis plan.

Confirmed ORR was 45.1% (20 CR, 49 PR) vs 33.1% (6 CR, 45 PR). Median (range) DOR was NR (2.3+ to 53.5+) vs 10.6 mo (2.8 to 48.3+), respectively. Treatment-related adverse events (TRAEs) occurred in 79.7% vs 98.6% of pts; 21.6% vs 66.4%, respectively, had grade ≥3 TRAEs.

Two-year update from CheckMate 9LA 

https://meetinglibrary.asco.org/record/196799/abstract 

At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%.

Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively.

ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology.

Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively.

Updated overall survival (OS) results from the phase III MONALEESA-3

https://meetinglibrary.asco.org/record/198455/abstract

Overall survival (OS) Updated analyses from PALOMA-3

https://meetinglibrary.asco.org/record/198379/abstract

Phase 2 results of the ZUMA-3 

https://meetinglibrary.asco.org/record/195802/abstract

As of 9/2020, 55 of 71 enrolled pts received KTE-X19, with a median follow-up of 16.4 mo (range, 10.3–22.1). Adverse events (AEs; n = 8) and ineligibility (n = 4) were the most common reasons enrolled pts did not receive KTE-X19 infusion. Median age was 40 y (range, 19–84), median BM blasts at screening were 65% (range, 5–100), and 47% of pts had ≥3 prior therapies, with 45%, 22%, and 42% having previously received blinatumomab, inotuzumab ozogamicin, or allogeneic stem cell transplant (alloSCT), respectively. The CR/CRi rate was 71% (95% CI, 57–82; 56% CR, 15% CRi); 31% of responders had ongoing responses. Median (95% CI) DOR, RFS, and OS were 12.8 mo (8.7–not estimable [NE]), 11.6 mo (2.7–15.5), and 18.2 mo (15.9–NE), respectively. In responders, median (95% CI) RFS and OS were 14.2 mo (11.6–NE) and not reached (16.2–NE). The MRD– rate was 97% among pts with CR/CRi. Among 25 pts with prior blinatumomab treatment, the CR/CRi rate was 60%. Ten pts (18%) received subsequent alloSCT at a median 98 days post–KTE-X19 infusion. Median DOR remained unchanged when not censoring for alloSCT. Grade ≥3 AEs occurred in 95% of pts, most commonly anemia (49%) and neutropenia (49% [febrile 13%]). Grade ≥3 cytokine release syndrome (CRS; per Lee at al. Blood 2014) and neurologic events occurred in 24% and 25% of pts, respectively, and were generally reversible. Two Grade 5 KTE-X19–related events occurred (brain herniation, n = 1; septic shock, n = 1). Median times to onset of CRS and neurologic events were 5 d and 9 d, with median durations of 7.5 d and 7 d, respectively. Median peak CAR T-cell levels (cells/µL) were 40.5 (range, 1.3–1533.4) in pts with CR and 0 in nonresponders. CAR T cells were undetectable by 9 mo in ongoing responders.

Primary analysis of the phase 2 Elara trial：Tisa-cel in RR FL

https://meetinglibrary.asco.org/record/196296/abstract

As of September 28, 2020, 98 pts were enrolled and 97 received tisa-cel (median follow-up, 10.6 mo). At study entry, median age among treated pts was 57 y (range, 29-73), 85% had stage III-IV disease, 60% had a FLIPI score ≥3, 65% had bulky disease, and 42% had LDH > upper limit of normal.

The median number of prior therapies was 4 (range, 2-13); 78% of pts were refractory to their last treatment (76% to any ≥2 prior regimens) and 60% progressed within 2 y of initial anti-CD20–containing treatment.

Of 94 pts evaluable for efficacy, the CRR was 66% (95% CI, 56-75) and the ORR was 86% (95% CI, 78-92). CRRs/ORRs were comparable among key high-risk subgroups.

Estimated DOR (CR) and PFS rates at 6 mo were 94% (95% CI, 82-98) and 76% (95% CI, 65-84), respectively.

Of 97 pts evaluable for safety, 65% experienced Gr ≥3 adverse events within 8 weeks post-infusion, most commonly neutropenia (28%) and anemia (13%). Any-grade cytokine release syndrome (per Lee scale) occurred in 49% of pts (Gr ≥3, 0%).

Any-grade neurological events (per CTCAE v4.03) occurred in 9% of pts (Gr 3, 0%; Gr 4, 1 pt and recovered). Three pts died from progressive disease. Cellular kinetic parameters for tisa-cel were estimated using transgene levels (by qPCR) in peripheral blood.

Cmax and AUC0-28d were similar between responders (CR or partial response) and non-responders (stable or progressive disease). Maximum transgene levels were reached by a median of 10 days in responders and 12.9 days in non-responders; transgene persistence was detected up to 370 days and 187 days, respectively.

Ciltacabtagene autoleucel (cilta-cel)

Updated results from CARTITUDE-1

https://meetinglibrary.asco.org/record/195437/abstract

Results: As of Sept 1, 2020, 97 pts with a median of 6 prior lines received cilta-cel. Overall response rate per independent review committee (primary endpoint) was 97% (95% CI, 91–99), with 67% achieving stringent complete response (sCR). Median time to first response was 1 month (range, 1–9), and median time to CR or better was 2 months (range, 1–15). Responses deepened over time, and median duration of response was not reached.

Of 57 pts evaluable for minimal residual disease (MRD) assessment, 93% were MRD-negative at 10-5.The 12-month progression-free survival (PFS) and overall survival rates (95% CI) were 77% (66–84) and 89% (80–94), respectively; median PFS was not reached.

Grade 3/4 hematologic AEs ≥20% included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%).

CRS occurred in 95% of pts (4% grade 3/4), with median time to onset of 7 d (range, 1–12), and median duration of 4 d (range, 1–14, excluding 1 pt with 97-d duration). CRS resolved in all but one with grade 5 CRS/haemophagocytic lymphohistiocytosis.

CAR T-cell neurotoxicity occurred in 21% of pts (grade ≥3, 10%). Fourteen deaths occurred during the study after cilta-cel infusion: none within the first 30 days, 2 within 100 days; and 12 more than 100 days post infusion, of which 5 were due to disease progression, and 4 due to treatment-related AEs.

Comparison of outcomes with cilta-cel in CARTITUDE-1 vs RWSOC

https://meetinglibrary.asco.org/record/195465/abstract

CARTITUDE-2: Efficacy and safety of  cilta-cel in patients with progressive MM after one to three prior lines of therapy

https://meetinglibrary.asco.org/record/195446/abstract

As of Feb 2021 data cutoff (median follow-up: 5.8 months [mo]; range: 2.5–9.8 mos), 20 pts (65% male; median age 60 years [38–75]) received cilta-cel; 1 pt was treated in an outpatient setting.

Pts received a median of 2 prior LOT (1–3); 12 pts received < 3 prior lines and 8 received 3 prior LOT. All pts were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab.The majority (95%) were refractory to the last LOT; 40% were triple refractory.

Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved stringent CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR.

Median time to first response was 1.0 mo (0.7–3.3); median time to best response was 1.9 mo (0.9–5.1). Median duration of response was not reached. All pts (n = 4) with MRD-evaluable samples at 10-5 at data cutoff were MRD-negative.

Hematologic AEs ≥20% were neutropenia (95%; gr 3/4: 90%), thrombocytopenia (80%; gr 3/4: 35%), anemia (65%; gr 3/4: 40%), lymphopenia (60%; gr 3/4: 55%), and leukopenia (55%; all gr 3/4).

CRS occurred in 85% of pts; 10% were gr 3/4. Median time to CRS onset was 7 d (5–9), with a median duration of 3.5 d (2–11). CAR T-cell neurotoxicity occurred in 20% of pts (all gr 1/2).

Three pts had ICANS (1 gr 1; 2 gr 2); median time to onset was 8 d (7–11) and median duration was 2 d (1–2). One pt had gr 2 facial paralysis; time to onset was 29 d with a duration of 51 d.

One death occurred due to COVID-19 (assessed as treatment (tx)-related by investigator). Safety profile was manageable in the pt treated in an outpatient setting.

ESCORT-1st：Camrelizumab in 1L ESCC

https://meetinglibrary.asco.org/record/195933/abstract

主要终点OS和PFS均显著提升：

  • OS 15.3 mo vs 12.0 mo; HR, 0.70  单侧P = 0.0010

  • PFS 6.9 mo vs 5.6 mo; HR, 0.56 单侧P < 0.0001

其他终点

  • ORR 72.1%  vs 62.1%，DoR 7.0 vs 4.6 mo

  • ≥Gr3 TRAE 63.4% vs 67.7%

Camrelizumab+GP in 1L RM NPC

https://meetinglibrary.asco.org/record/196366

主要终点PFS per IRC显著提升：10.8 months vs  6.9 mo HR 0.51 单侧P < 0.0001

其他终点

  • ORR per IRC 88.1% vs 80.6%，DoR 9.9 vs 5.7 mo HR 0.48

  • OS 1NR vs 22.6 months; HR 0.67

  • ≥Gr3 TRAE 93% vs 90%

Camrelizumab+Fami+nab-P in 1L TNBC

https://meetinglibrary.asco.org/record/196659/abstract

SHR-1701：PD-L1xTGFb

https://meetinglibrary.asco.org/record/200062

17 pts (1 mg/kg Q3W [n = 1]; 3, 10, 20 and 30 mg/kg Q3W [n = 3 each]; 30 mg/kg Q2W [n = 4]) were enrolled in dose escalation part. No DLT was observed and MTD was not reached. Another 32 pts (10 mg/kg Q3W [n = 8]; 20 and 30 mg/kg Q3W [n = 9 each]; 30 mg/kg Q2W [n = 6]) were enrolled in dose expansion part. Of 49 enrolled pts, 33 pts (67.3%) had received ≥2 lines of prior systemic therapy. As of data cutoff on Oct 30, 2020, the median duration of SHR-1701 exposure was 6.0 weeks (range, 2.0-78.6). The most common reported TRAEs were increased ALT/AST, anemia, hypothyroidism, and increased bilirubin/conjugated bilirubin, with incidence > 15%. The incidence of irAEs reported by the investigator was 46.9% and 4 pts received systemic corticosteroids. Hypothyroidism and rash were the most common irAEs with incidence > 10%. The incidence of Grade ≥3 TRAEs was 18.4%. The incidence of Grade ≥3 irAEs was 10.2%. 1 pt suffered early death for liver failure more likely caused by tumor progression. PK analysis showed a linear dose-exposure relationship with SHR-1701 dosing from 1 to 30 mg/kg. The peripheral PD-L1 target occupancy rate exceeded 90%, and nearly complete TGF-β1 trapping was detected in all dose groups. Of 49 enrolled pts, 45 pts completed at least once efficacy evaluation. The ORR was 17.8% (95% CI, 8.0%-32.1%), with 8 pts achieving PR (2 lung adenocarcinoma, 1 HCC, 1 ESCC, 1 dMMR-CRC, 1 renal cancer, 1 epiglottis cancer, and 1 pancreatic acinar cell carcinoma). The DCR was 40.0% (18/45; 95% CI, 25.7%-55.7%). Majority of responses (7/8) were still ongoing, and the median DoR had not been reached yet. Based on data of saftety, PK, PD, and efficacy, we recommended 30 mg/kg Q3W as the RP2D.

Dalpiciclib in 2L HR+ HER2- ABC

https://meetinglibrary.asco.org/record/195721

Dalpiciclib+ FUV vs PBO + FUV in 内分泌治疗后进展的HR+ HER2- ABC，主要终点研究者评估的PFS 15.7  vs 7.2 mo HR, 0.42 ; P < 0.0001，TFSCT同样也显著延长：HR, 0.47 P < 0.0001，OS尚未成熟，药物暴露时间：Dalpiciclib+ FUV 组中Dalpiciclib 9.4mo、FUV 9.9mo，PBO+FUV组中FUV 6.1mo

主要≥Gr3 TRAE包括中性粒细胞减少84.2%vs 0%和淋巴细胞减少62.1% vs 0%，但因AE引起的治疗终止2.5%  vs 3.3% 及 SAE 5.8%  vs 6.7% 略低

Toripalimab plus axitinib in resectable mucosal melanoma

https://meetinglibrary.asco.org/record/196429/abstract

the pathologic response rate was 28.6% (4/14, 2 pCR, 2pPR)

Lenvatinib plus toripalimab 一线肝内肝管癌

https://meetinglibrary.asco.org/record/198873/abstract

From March 2020 to Sep. 2020, 31 pathologically confirmed advanced ICC pts with a mean age of 58.4 (range, 25-73) years, including 18 women (58.0%), were enrolled at Zhongshan Hospital, Fudan University.

At the end of last follow-up (February 10, 2021), the ORR was 32.3% (10/31; 95% CI: 16.7%-51.4%) and the disease control rate (DCR) was 74.2% (23/31; 95% CI: 55.4%-88.1%).

Median follow-up was 6.9 months. Two pts with locally advanced disease were down-staged and then underwent resection. They remained disease-free survival at the end of last follow-up. 11 pts exerted disease progression and 7 pts died.

The median PFS and OS have not been reached. Median duration of response (DOR) has not been reached and responses were ongoing in 9/10 (90.0%) pts at data cutoff. 6-months OS rate was 87.1%.

No grade 5 adverse event (AE) was observed in present study. 32.3% (10/31) of pts experienced Grade 3 or higher AEs and 1 pts discontinued the treatment owing to severe fatigue.

IBI110 (anti-LAG-3 mAb)/IBI-110+ SINTILIMAB

https://meetinglibrary.asco.org/record/196047/abstract

Phase Ia mono: 21 pts (median age: 62 yr [range 43-72]; ECOG PS: 0 [n = 11], 1 [n = 10]) were enrolled. Dose escalation has completed and no dose-limiting toxicity (DLT) was observed in all dose cohorts. The most common treatment-related adverse event (TRAE) was anaemia (19.0%). TRAEs ≥G3 included anaemia (4.8%), ascites (4.8%) and hepatic function abnormal (4.8%). By investigator-assessment, best response was 1 confirmed partial response (PR) (ovarian cancer, 3 mg/kg IBI110 single agent) and 5 stable disease (SD) in monotherapy. After crossing from mono to combo at progression, 5 pts were observed to have SD.

Phase Ib combo: 12 pts (median age: 60 yr [range 33-72]; ECOG PS: 0 [n = 7], 1 [n = 5]) were enrolled. All dose cohorts in dose escalation except IBI110 5mg/kg+ sintilimab have completed DLT observation and no DLT was observed. The most common TRAE was AST increased (41.7%). TRAEs ≥G3 included hyperglycaemia (8.3%), bilirubin conjugated increased (8.3%) and hepatic function abnormal (8.3%). By investigator-assessment, best response was 2 PR (small cell lung cancer and endometrial cancer) and 6 SD.

Fruquintinib plus sintilimab in advanced colorectal cancer

https://meetinglibrary.asco.org/record/199716/abstract

As of Jan 5, 2021, 44 CRC pts which failed to at least 2 previous lines of therapy containing fluoropyrimidine, oxaliplatin or irinotecan were enrolled. They received either 5mg-intermittent or 3mg-continous dosage (n = 22, each), the ORR was 22.7% (10/44, 95% CI: 11.5-37.8%) with 27.3% (6/22, 95% CI: 10.7-50.2%) in 5mg-intermittent group and 18.2% (4/22, 95% CI: 5.2-40.3%) in 3mg-continuous group. With a median follow-up time of 8.3 (range: 0-9.6) months, the K-M estimated median PFS was 6.8 (95% CI:5.6-NA) months and 4.3 (95% CI:3.5-NA) months for 5mg-intermittent group and 3mg-continuous group, respectively. Overall, 60 pts were enrolled for safety analysis, including 23 in stage1 and 37 (only CRC) in stage 2. In stage 1, all pts experienced TEAEs, 52.2% of which were ≥ grade 3. The most frequently reported TEAEs were TSH increasing (73.9%), fecal occult blood positive (56.5%), and Palmar-plantar erythrodysaesthesia syndrome (PPES) (56.5%). SAEs occurred in 8 (34.8%) pts and no treatment-related death was reported. One patient in Cohort B reported manageable DLT. In stage 2, all pts experienced TEAEs, 18 (48.6%) pts experienced ≥ grade 3 TEAEs with 6 (31.6%) in 5mg-intermittent group and 12 (66.7%) in 3mg-continuous group. The most common TEAEs were proteinuria (45.9%) and TSH increasing (37.8%). TEAEs leading to either fruquintinib or sintilimab discontinuation occurred in 3 (5%) pts each.

anti-TIGIT ociperlimab

AdvanTIG-202：http://meetinglibrary.asco.org/record/201291/abstract

AdvanTIG-203：https://meetinglibrary.asco.org/record/201241/abstract

aumolertinib in 1L EGFRm NSCLC

https://meetinglibrary.asco.org/record/198410/abstract

PFS 19.3 vs 9.9 mo, HR 0.46, p<0.0001

Results:

On January 7, 2021, 35 pts had been enrolled and treated with lisaftoclax at doses ranging from 20 to 1,200 mg, with a median (range) of 2 (1-13) prior lines of treatment, and had diagnoses of R/R CLL or SLL (n = 15), MM (n = 6), FL (n = 5), WM (n = 4), and either AML, MCL, DLBCL, MDS, or HCL (n = 1 each).

No DLT has been observed, even though 1,200 mg was considered as the highest dose treated. The MTD has not been reached, and no laboratory or clinical TLS has been reported.

Any grade TRAEs in > 10% of pts included neutropenia (22.9%) and anemia (17.1%; hematologic), and fatigue (28.6%), diarrhea (17.1%), and nausea (11.4%; nonhematologic). Grade >3 TRAEs were neutropenia (14.3%) and thrombocytopenia, leukopenia, lymphopenia, fatigue, and nausea (2.9% of pts each).

In CLL/SLL pts, grade 3-4 TRAEs included neutropenia (13.3%) and thrombocytopenia (6.7%), which did not cause treatment-related discontinuation.

In all, 12 of 35 pts (34.3%) had non-treatment-related SAEs, and only two pts experienced > 1 SAE.

With a median (range) treatment of 7 (3-20) cycles, 12 of 14 evaluable R/R CLL/SLL pts achieved PR, for an ORR of 85.7% and a median (range) time to response of 3 (2-7) cycles.

Absolute lymphocyte counts (ALCs) were reduced at lisaftoclax doses as low as 20 mg/day. The preliminary PK profile showed that exposures increased with lisaftoclax doses from 20 to 1,200 mg (average half-life: 4-5 hours). On BH3 profiling, lisaftoclax rapidly triggered changes in BCL-2 complex in CLL/SLL pt samples, which were consistent with rapid clinical reductions in ALCs.

Conclusions:

Lisaftoclax was well tolerated up to 1,200 mg/day. No TLS was observed, even with the daily ramp-up schedule. There were no significant new or unmanageable safety findings, and the ORR in R/R CLL/SLL pts was 85.7%. Grade 3-4 TRAEs were infrequent, even at dose levels of 800 mg and above. BCL-2i lisaftoclax offers a treatment alternative for patients with R/R CLL/SLL and other HMs, with a daily ramp-up schedule that may be more pt “user friendly” and a favorable preliminary safety profile. Internal study identifier APG2575-001. Clinical trial information: NCT03537482

Preliminary results of a phase II study of alrizomadlin (APG-115)

https://meetinglibrary.asco.org/record/196027/abstract

AK112 in  advanced solid tumors

https://meetinglibrary.asco.org/record/200093/abstract

Penpulimab plus anlotinib in 1L uHCC

https://meetinglibrary.asco.org/record/194390/abstract

Penpulimab plus anlotinib in 1L nsqNSCLC

https://meetinglibrary.asco.org/record/201091/abstract

ARX788

Safety and unique pharmacokinetic profile of ARX788, a site-specific ADC, in heavily pretreated patients with HER2-overexpresing solid tumors: Results from two phase 1 clinical trials.

https://meetinglibrary.asco.org/record/197084/abstract

69 and 34 heavily pretreated patients received ARX788 monotherapy in the ACE-Breast-01 (median 6 prior lines of therapy) and ACE-Pan tumor-01 trial (including breast, gastric/GEJ, NSCLC, ovarian, urothelial, biliary track, endometrial, and salivary gland cancer) respectively. Dose escalation for both studies have been completed with no DLT reported. MTD has not been reached. ARX788 was generally well tolerated with most AEs being grade 1 or 2. The most common grade >3 AEs include ocular AEs (5.7 %) and pneumonitis (4.3%) in the ACE-Breast-01 trial; pneumonitis (2.9%) and fatigue (2.9%) in the ACE-Pan tumor-01 trial. Low systemic toxicities in terms of the incidence rate and grade (as shown in table). No treatment-related death. In the 1.5 mg/kg cohort, ORR was 74% (14/19) and 67% (2/3) for ACE-Breast-01 and ACE-Pan tumor-01, respectively. DCR was 100%. Median DOR or median PFS has not been reached. PK profiles for total antibody and ARX788 were generally comparable across all dose levels. Mean T1/2 for ARX788 and total antibody had approximately 100 hours at the dose of 1.5 mg/kg. Serum pAF-AS269 concentrations peaked with a median time of 168 h. Serum exposure of pAF-AS269 was low with the Cmax and AUC at cycle 1 being approximately 0.1% and 0.18% of those for ARX788 on a molar basis, respectively.

A phase 1 multicenter, dose expansion study of ARX788 as monotherapy in patients with HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma (ACE-Gastric-01).

https://meetinglibrary.asco.org/record/199351/abstract

RC48-ADC combined with toripalimab in mUC

https://meetinglibrary.asco.org/record/197483/abstract

As of 8 Jan 2021 (data cutoff), 14 mUC pts (9 males, median age 66 y [52-76]) were enrolled. Most pts were systemic treatment naïve (57%) in the locally advanced or metastatic setting. The primary site was in upper tract UC in 50%; 50% had visceral metastases (mets), including 36% with liver mets; HER2 expression was positive (IHC 3+ or 2+ ISH+) in 28%, and 43% PD-L1 CPS≥10. A total of 36 pts is anticipated to be enrolled by Apr 2021. No dose limiting toxicity was reported and the recommended dose for RC48-ADC was 2mg/kg. At data cutoff, 10/14 patients were evaluable for response, with 8 PR, 1 SD (tumor shrinking), and 1 PD. The objective response rate (ORR) was 80%, and disease control rate (DCR) was 90%. All responsive patients have durable efficacy and are still on treatment. Follow-up continues for PFS and OS. Most common treatment-related AEs were grade 1-2, including aminotransferase level increased (7/14, 50%), weight loss (6/14, 43%), alopecia (6/14, 43%), asthenia (4/14, 29%), anemia (3/14, 21%), leukopenia (21%), peripheral sensory neuropathy (21%), hypothyroidism (21%), blood triglycerides increased (21%), and creatine phosphokinase increase (21%). One pt had G3 intestinal obstruction attributed to study drug and went back to treatment after recovery.

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