2023 Pre-ASCO Report
May 2023

Brought to you by:Summary
Abstracts from the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO) were released May
25th at 5pm EDT. The 2023 ASCO meeting will be held in Chicago from June 2-6, 2023.
We have highlighted some key abstracts with analyses. Included at the end of the report is a list of the ASCO data
events we have added from the Thursday release and Friday morning announcements. While this is just a brief
overview, we will be available to discuss any data of interest in further detail. Please email Biomedtracker.
Additionally, keep an eye out for our ASCO weekend updates and live-coverage when the meeting takes place.
As a reminder, our ASCO coverage will continue throughout the conference and beyond. Our coverage will include:
June 4 – ASCO Weekend Update
Shortly following the conference – Post-ASCO Report andPodcastJune 19 – Post-ASCO Webinar•••

About the Author
Biomedtracker is an independent research service that offers proprietary clinical assessments and patient-based
revenue forecasts of developmental drugs within a comprehensive and intuitive drug information database. Clientsfrom the pharmaceutical, biotech, and investment industries rely on Biomedtracker for its insight on the likelihood of
approval, commercial potential, and future data and regulatory catalysts for drugs within the competitive landscape ofevery important disease and indication. Over the last several years, Biomedtracker has become the leader inproviding objective information alongside evidence-based clinical assessments and investment research on pipeline
drugs worldwide. For more information on getting direct access to Biomedtracker, please email
BiomedSupport@sagientresearch.com.

Disclaimer
Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company
This report is published by Citeline (the Publisher). This report contains information from reputable sources andalthough reasonable efforts have been made to publish accurate information, you assume sole responsibility for theselection, suitability and use of this report and acknowledge that the Publisher makes no warranties (either express or
implied) as to, nor accepts liability for, the accuracy or fitness for a particular purpose of the information or advice
contained herein. The Publisher wishes to make it clear that any views or opinions expressed in this report byindividual authors or contributors are their personal views and opinions and do not necessarily reflect theviews/opinions of the Publisher.

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Table of Contents
BREYANZI FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL CELL LYMPHOCYTIC LYMPHOMA (SLL) – NHL…….4
VENCLEXTA FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL CELL LYMPHOCYTIC LYMPHOMA (SLL) – NHL…..8
VECTIBIX FOR COLORECTAL CANCER (CRC)…………………………………………………………………………10
ENHERTU FOR COLORECTAL CANCER (CRC)………………………………………………………………………...13
TECENTRIQ FOR COLORECTAL CANCER (CRC)………………………………………………………………………15
DKN-01 FOR GASTRIC CANCER……………………………………………………………………………………...18
TECENTRIQ FOR HEPATOCELLULAR (LIVER) CANCER (HCC) (INCLUDING SECONDARY METASTASES)……………….22
IMJUDO FOR HEPATOCELLULAR (LIVER) CANCER (HCC) (INCLUDING SECONDARY METASTASES)…………………..24
REBLOZYL FOR MYELODYSPLASTIC SYNDROME (MDS)………………………………………………………………26
AB-101 (ARTIVA) FOR NON-HODGKIN'S LYMPHOMA (NHL)………………………………………………………….30
TALZENNA FOR PROSTATE CANCER…………………………………………………………………………………..32
LENVIMA FOR RENAL CELL CANCER (RCC)…………………………………………………………………………..35
CABOMETYX / COMETRIQ FOR RENAL CELL CANCER (RCC)…………………………………………………………38
LIST OF BIOMEDTRACKER ASCO ABSTRACT NIGHT EVENTS…………………………………………………………40

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Breyanzi for Chronic Lymphocytic Leukemia (CLL)/Small Cell
Lymphocytic Lymphoma (SLL) - NHL
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase I/II - TRANSCEND-CLL-004

Market Group:

Oncology

Lead Company:

Bristol Myers Squibb Company (BMY)

Partner Companies:

N/A
CelgeneFormer Companies:

Juno Therapeutics

Change to Likelihood of Approval:

1%

Likelihood of Approval:

15% (4% Above Avg.)

Average Approval:

11%

Treatment Description

Number of Patients
Number of Evaluable
Patients

Treatment

Breyanzi (Primary Efficacy Analysis Set at

Breyanzi (Full Efficacy Set at

DL2)

DL2)

49

87

N/A

N/A

Complete Response Rate

18.4 %(Endpoint=Primary)(P=0.0006)

Objective Response Rate

42.9 %(Endpoint=N/A)(P=0.3931)

uMRD in Blood(Endpoint=N/A)
uMRD in Marrow(Endpoint=N/A)

4

Treatment

18.4 %

47.1 %

63.3 %

64.4 %

59.2 %

58.6 %

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Progression-Free Survival(Endpoint=N/A)

11.9 Months

18.0 Months

Bristol Myers Squibb announced the presentation of data from the primary analysis of the Phase I/II TRANSCEND CLL 004
study of Breyanzi (lisocabtagene maraleucel) in patients with relapsed or refractory chronic lymphocytic leukemia or small
lymphocytic lymphoma at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The abstract entitled"Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL):
Primary analysis of TRANSCEND CLL 004" will be presented at the meeting on June 6, 2023.
Data from this study were last seen in January 2023.
Context
Results from TRANSCEND CLL 004 will be discussed with health authorities.
DesignTRANSCEND CLL 004 is a Phase I/II open-label, multicenter study evaluating Breyanzi in patients with relapsed or
refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The Phase I dose escalation portion of the study
assessed the safety and recommended dose for the subsequent Phase II expansion cohort. The Phase II portion of thestudy is evaluating Breyanzi at the recommended dose from the Phase I monotherapy arm.
The TRANSCEND CLL 004 trial included a broad population of patients with relapsed or refractory CLL or SLL with highunmet need who had received at least two prior lines of therapy, including a BTKi (n=117). The prespecified primary
efficacy analysis set (PEAS; n=49) consisted of a subset of patients who had experienced disease progression following
treatment with a BTKi and failure of BCL2i-based regimens, representing a patient population with advanced andaggressive disease, and who were treated with the target dose of 100 x 106 CAR-positive viable T-cells of Breyanzi.
Endpoints
The primary endpoint of the Phase II portion of the study was complete response rate, including complete remission withincomplete bone marrow recovery, based on independent review committee according to the International Workshop on
Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines.
Results
High rates of undetectable minimal residual disease (uMRD) were observed across patients treated with Breyanzi, with auMRD rate 63.3% in the blood (95% CI: 48.3-76.6) and 59.2% in the bone marrow (95% CI: 44.2-73.0), which was
associated with an increase in progression-free survival. The overall response rate (ORR) was 42.9% (95% CI: 28.8-57.8;
p=0.3931), with a median duration of response of 35.3 months (11.01-NR). Data were consistent between the PEAS andthe broad patient population evaluated in the study, including heavily pretreated patients with a median of five prior lines oftherapy (2 – 12) and high-risk disease, with a CR rate of 18.4% (95% CI: 10.9-28.1), demonstrating the clinical benefitof Breyanzi for a broad patient population with relapsed or refractory CLL or SLL.
At a median follow-up of 21.1 months, results show that Breyanzi delivered statistically significant complete response (CR)rates, the study’s primary endpoint, in 18.4% of patients in the primary efficacy analysis set (95% CI: 8.8-32; p=0.0006).
Most Common Adverse Events
Among all treated patients in the study (n=117), including subgroups of heavily pretreated patients, Breyanzi exhibited amanageable safety profile, and no new safety signals were observed. Any grade cytokine release syndrome (CRS)
occurred in 84.6% of patients, with Grade 3 CRS occurring in 8.5% of patients. No Grade 4/5 CRS events were reported.
Any grade neurologic events (NE) were reported in 45.3% of patients, with Grade 3 NE reported in 17.9% of patients andone case (0.9%) of Grade 4 NE reported. No Grade 5 NE were reported. Among patients who achieved a CR, no diseaseprogression or deaths were observed, with median duration of response not reached.

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)

Conclusion
Per the abstract, Breyanzi demonstrated durable CR/CRi, high uMRD rates, and a manageable safety profile in pts withheavily pretreated, high-risk R/R CLL/SLL and high unmet need.

Comment
CAR T-cell therapy has shown impressive success within B-cell malignancies with approvals for aggressive diseases
such as diffuse large B cell lymphoma (DLBCL) and acute lymphoblastic leukemia, however, surprisingly it's story inchronic lymphocytic leukemia (CLL) has, until now, been largely underwhelming. Data released in the ASCO 2023
abstract from the Phase I/II TRANSCEND-004 trial, investigating Breyanzi - Bristol Myers Squibb's CD19-directed
CAR T-cell therapy, in multi-refractory CLL patients mark the first positive results for a CAR-T cell therapy in the CLL
space. In January this year, it was announced the study

met the primary endpoint of complete response ratecompared to historical control in the prespecified subset of patients with relapsed/refractory CLL that was refractory
to a BTK inhibitor and pretreated with a BCL-2 inhibitor. The release of numerical data demonstrates 18.4% of
patients, both in the primary efficacy cohort and broad patient population group, achieved complete responses, withmedian duration of response unreached at 21.1 months follow up. The median number of prior therapies for thispopulation was five, and an achievement of an 18.4% complete response rate in such highly-refractory patients isremarkable. Despite current therapies providing patients with life expectancies which rival that of an age-matchedgeneral population, the potential to offer deep and durable remissions remains a major area of unmet need in CLL especially within patients who have failed on both a BTKi and BCL2i. Armed with these data from TRANSCEND,
Breyanzi looks primed to potentially address this need and reform the heavily pre-treated landscape for CLL
patients.
However, TRANSCEND's design may cause bumps in Breyanzi's road to approval. The single-arm nature of the trial
may pose as a limitation, with FDA chief Califf calling for a reform of the accelerated approval pathway amongst
other top officials advocating for limited use of single arm trials. Although Califf did recognise that single-arm trials
can sometimes be necessary, such as in rare diseases where there are no other effective treatments for comparison,
which may act as a saving grace for TRANSCEND. Another concern for the trial is that the primary efficacy data isderived from a small sample population of only 49 patients. Breyanzi previously achieved accelerated approval in
DLBCL based off response data from a single arm trial, however the population size much larger with 256 evaluable
patients. The clinical benefit of Breyanzi in DLBCL was also arguably a lot more prominent, with a 53% complete
response rate and overall response rate of 73% from this trial. In the TRANSCEND data from the ASCO abstract, theoverall response rate in the primary efficacy group was reported at 42.9% and was not significant. Whilst thecomplete response data looks promising to offer transformative outcomes for heavily relapsed hard-to-treat CLL
patients, the complete dataset may not be compelling enough to outweigh the trial pitfalls to secure Breyanzi
accelerated approval. It may come unexpectedly if the FDA calls for more data in a larger patient population.
If Breyanzi is to be approved, it will enter the market largely uncontested, with currently limited treatment options for
CLL patients who progress following BTKi and BCL2i treatment. Eli Lilly's Jaypirca is currently in Phase III
investigation for this patient population and has shown impressive data thus far, and non-covalent BTKis are
beginning to look set to become the standard of care treatment for BTKi and BCL2i pre-treated patients, following
their approval. This would likely leave Breyanzi reserved for fourth line and beyond. However, where Jaypirca
struggles to compete with Breyanzi is in its complete response data, which will be the key differentiator for Breyanzi
and likely the driver behind physicians choice to prescribe the CAR T therapy as a third-line option.
Bristol Myers Squibb (BMS) announced at the 41st annual JP Morgan conference this year that they plan to file forapproval of Breyanzi in CLL in the upcoming year. Considering Breyanzi's launch into both European and Japanesemarkets for DLBCL, it can be assumed BMS will strategize the same approach to launch Breyanzi into all major

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)markets for CLL as well. The therapy, however, may face more of a struggle to pull uptake in single payer healthcare
markets due to the high cost of CAR T-cell therapy. Strong evidence that Breyanzi can offer durable remissions will
be imperative to justify the high cost treatment in these countries. In January 2023, Yescarta, a CD19-directed CAR
T-cell therapy, gained a positive recommendation from the National Institute for Health and Care Excellence (NICE)
for its use in refractory DLBCL, marking the first positive recommendation for a personalised immunotherapy. Thiswas supported by its impressive data in a poor prognosis and limited treatment disease space. Though Breyanzi's
complete response data is compelling considering the current lack of deep remissions attained with the current CLL
treatments, it remains questionable whether the complete dataset is strong enough to warrant cost effectiveness for
single payer systems. Nevertheless, these results from TRANSCEND represent one of the first strong indicators forthe plausibility of remission in multi-refractory patients and mark a breakthrough for CAR T-cell therapy within the
CLL space. We are raising the LOA by 1%.

Source:Business Wire 05/25/2023 (BMY)
American Society of Clinical Oncology (ASCO) (Abstract 7501)
Citeline Analysis 05/26/2023

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Venclexta for Chronic Lymphocytic Leukemia (CLL)/Small Cell
Lymphocytic Lymphoma (SLL) - NHL
Event Date:

05/25/2023

Event Type:

Trial Data - Top-Line Results (Clinical Analysis)

Trial Name:

Phase III - A041702 (w/Ibrutinib + Obinutuzumab; NCI)

Market Group:

Oncology

Lead Company:

AbbVie Inc. (ABBV)

Partner Companies:

Roche (RHHBY)Former Companies:

N/A

Change to Likelihood of Approval:

0%Likelihood of Approval:

100% (Same As Avg.)

Average Approval:

100%

Comparator

Treatment

Ibrutinib +Ibrutinib + Venetoclax +Obinutuzumab

Obinutuzumab

Number of Patients

N/A

N/A

Number of Evaluable Patients

N/A

N/A

87.5 %

85 %

29

35

Treatment Description

Median Progression-Free Survival at 14
MonthsEvents Observed

The abstract entitled "Results of a phase 3 study of IVO vs IO for previously untreated older patients (pts) with chronic
lymphocytic leukemia (CLL) and impact of COVID-19 (Alliance)" will be presented at ASCO on June 2-6, 2023.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
Context
The Alliance DSMB approved release of data on November 4, 2022 after meeting the protocol defined futility threshold at
the second planned event-driven interim analysis. Data were locked on December 15, 2022.
DesignAlliance for Clinical Trials in Oncology A041702 is a multicenter trial designed to evaluate if IVO with response-guided

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)discontinuation of I improves progression free survival (PFS) versus IO with indefinite I in treatment-naïve, older CLL pts.
IO is given in standard fashion, and in the IVO arm V is added at C3D1 and continued until C14D28. After 14 cycles, pts
undergo response evaluation including CT scans and bone marrow biopsy with central MRD assessment by flow
cytometry. Pts in IVO arm with uMRD CR discontinue I; all others continue I until progression or unacceptable toxicity.
Eligible pts were age ≥70 years (amended to ≥65). Pts had CrCl ≥ 40 mL/min, bilirubin ≤ 1.5 x ULN, and no otherlife-limiting intercurrent illness. Pts were stratified based on Rai stage and +/- del17p13.1 by FISH, and randomized 1:1 to
IO:IVO. With 431 evaluable pts, the trial had 90% power to detect significant improvement in PFS using a one-sided
log-rank test with one-sided type 1 error rate of 2.5%.
Results
Between January 4, 2019 and July 15, 2022, 465 pts were registered (IO:232, IVO:233). Median age was 74; 67% of pts
were men. Rai stage 3-4 was seen in 55% and del17p in 13%.
With median follow-up of 14 months, PFS of IO was 87.5% compared to 85% on IVO. Events were observed in 29 pts on IO(4 progressions, 23 deaths, 2 pts started other therapy) and 35 on IVO (7 progressions, 28 deaths). The predefined futility
boundary was crossed, with a hazard ratio (HR) of 1.20 (95% CI: 0.73-1.97) in favor of IO. COVID-19 was the leading causeof death in both arms, (11 COVID-19 deaths on IO, 19 on IVO), with 13 and 11 additional deaths from other causes,
respectively. Censoring pts with COVID-19 related deaths, PFS HR is 0.82 (95% CI: 0.44-1.53) in favor of IVO.
Most Common Adverse Events
Grade 3+ toxicity and discontinuation in year 1 of therapy were similar between arms.
Conclusion
This study demonstrates that PFS for IVO is not superior to IO for treatment-naive older CLL pts in the setting of the
COVID-19 pandemic. Study treatment is ongoing, and long-term follow-up will determine if there are advantages to IVO,
with special attention to MRD and therapy discontinuation.

Comment
These results from the Phase III Alliance trial come as a disappointment, with the triplet combination of Imbruvica,
Venclexta and Gazyva failing to improve progression free survival compared to the doublet of Venclexta and Gazyva
in first-line chronic lymphocytic leukemia (CLL). The disruption the COVID-19 pandemic has had on the data fromthis trial leaves uncertainty for the success of this combination regimen. The censoring of patients with COVID-19
related deaths leading to a shift in PFS HR in favor of IVO is a positive indication that the triplet regimen still has
potential to improve patient outcomes and warrants further investigation. Yet, the adjusted PFS HR of 0.82 suggests
only moderate benefit.
The safety information obtained, despite the tribulations of this trial, is positive, with grade 3+ toxicity anddiscontinuation rates reported to be similar between both arms. This could be considered a small win for the
combination therapy as it may work towards dispelling physician concerns over the additional toxicity that comeswith using a triplet regimen. However, unless long-term follow-up data can reveal IVO to significantly improve
undetectable minimal residual disease and extend progression free survival, these safety data remain trivial.
In 2022, the Phase III GLOW trial, which evaluates Imbruvica and Venclexta combination in treatment naïve CLL
patients, met its primary endpoint and subsequently secured European approval. This represented the first BTKi andBCL2i combination regimen to enter the market. However, its uptake has been lackluster, with many physicians
expressing concerns of front-loading treatment. Moreover, AbbVie has not announced any plans to file a regulatory
submission for the doublet regimen to the FDA. Considering the underwhelming traction the doublet therapy hasreceived across markets, it begs to question how successful a triplet regimen would be. In order for IVO to
differentiate itself and prove to be a compelling therapy it will likely need to demonstrate deep and durable
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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)differentiate itself and prove to be a compelling therapy it will likely need to demonstrate deep and durable
remissions for patients, which cannot be obtained by the use of Imbruvica monotherapy or Venclexta and Gazyva
combination. Long-term data will be imperative to determine this, however, considering these results at ASCO, it
does not look promising.
Other triplet BTKi + BCL2i + CD20 monoclonal antibody regimens are also being evaluated in CLL and have also
demonstrated disappointing results thus far. The triplet regimen of Calquence, Gazyva and Venclexta is being
investigated in the front-line and relapsed/refractory settings in various Phase II and Phase III trials. In late 2021, aPhase II study exploring this triplet regimen in frontline patients failed to meet its primary endpoint of undetectable
minimal residual disease in the bone marrow. Collectively, the data does not currently bode well for triplet regimens
and their future within the CLL space is uncertain. The Phase III ACE-CL-311 trial investigating Calquence, Gazyva
and Venclexta in front-line CLL patients is due to read-out this year and may serve as a clearer indication for how
triplet regimens will fit into the CLL treatment landscape.

Source:American Society of Clinical Oncology (ASCO) 05/25/2023 (Abstract 7500)
Citeline Analysis 05/26/2023

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Vectibix for Colorectal Cancer (CRC)
Event Date:

05/25/2023

Event Type:

Trial Data - Final Results (Clinical Analysis)

Trial Name:

Phase III - PARADIGM

Market Group:

Oncology

Lead Company:

Amgen, Inc. (AMGN)
Beta Pharma

Partner Companies:

Takeda Pharmaceutical (TAK)Former Companies:

N/A

Change to Likelihood of Approval:

0%Likelihood of Approval:

100% (Same As Avg.)

Average Approval:

100%

The abstract entitled "Efficacy of panitumumab in patients with left-sided disease, MSS/MSI-L, and RAS/BRAF WT: A
biomarker study of the phase III PARADIGM trial." will be presented at ASCO on June 2-6, 2023.
Data from this study were last seen in April 2023.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
DesignBaseline plasma circulating tumor DNA (ctDNA; >10 ng/mL and >10 nM DNA) from patients (pts) enrolled in the biomarker
study was assessed using a custom panel (PlasmaSELECT-R 91, PGDx). The efficacy (OS, progression-free survival [PFS],
response rate [RR], and curative resection rate [R0]) of PAN plus mFOLFOX6 compared with BEV plus mFOLFOX6
according to RAS, BRAF (V600E), and MSI status and primary tumor location was evaluated.
Results
Among 802 pts in the full analysis set, 733 (91%) had evaluable pretreatment samples for ctDNA analysis. Of these pts, 53(7.2%) and 78 (10.6%) pts had RAS and BRAF (V600E) mutations, respectively, and 20 (2.7%) pts had MSI high (MSI-H)
status. In left-sided mCRC pts with MSS/MSI-L and RAS/BRAF WT, OS tended to be longer with PAN vs BEV (40.6 [95%CI, 36.3-44.4] vs 34.8 [95% CI, 31.3-41.2] months, respectively; HR, 0.79 [95% CI, 0.64–0.97]). Although PFS wascomparable between PAN (13.6 months [95% CI, 12.6–15.3]) and BEV (12.6 months [95% CI, 11.3–14.1]; HR, 0.95 [95%CI, 0.77–1.17]), RR and R0 resection rates were higher with PAN (RR: 83.2% [95% CI, 78.0–87.6]; R0: 18.8% [95% CI:
14.2–24.1]) compared with BEV (RR: 66.4% [95% CI, 60.0–72.3]; R0: 10.0% [95% CI: 6.5–14.5]). OS was similar or inferior
to PAN vs BEV regardless of the primary sidedness in pts with MSI-H or RAS/BRAF mutations.
Conclusion
These results support PAN + mFOLFOX6 as a first-line therapy for left-sided pts with MSS/MSI-L and RAS/BRAF WT

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Comment
Set up to demonstrate Vectibix’s superiority to bevacizumab when added to first-line chemotherapy in KRAS/NRAS
wild-type colorectal cancer, the PARADIGM trial led to slightly more questions than answers. Results from the trial
were presented one year ago at ASCO 2022 and showed that Vectibix + mFOLFOX6 led to a statistically significant
OS improvement in both the left-sided primary tumor population, as well as in the intent-to-treat population versus
bevacizumab + mFOLFOX6. OS is confounded by subsequent therapies, although the post-progression systemictreatments were well balanced between the trial’s arms. However, median PFS values observed in PARADIGM were
not different in the two arms of the trial, and sidedness was not used as a stratification factor. In addition, thetrial recruited only Japanese patients, and although the study’s authors indicated that the results should not differ inWestern patients, the applicability of the results to the Western population may need to be verified.
In a bid to assess potential biomarkers and tease out any patient populations that may benefit more from the additionof Vectibix to mFOLFOX, multi-omics analyses of plasma circulating tumor DNA samples were conducted, with theresults presented at the ASCO 2023 meeting. The data indicate that left-sided mCRC patients with MSS/MSI-L andRAS/BRAF WT tumors benefited more from the addition of Vectibix (mOS: 40.6 months vs. 34.8 months forbevacizumab), thus supporting the use of Vectibix over bevacizumab in this patient population. In MSI-H or
RAS/BRAF mutated tumors (regardless of sidedness), the OS values in the Vectibix arm were similar or inferior tothose for bevacizumab. It remains to be seen, however, whether physicians will make the switch from what has been
the standard of care in the first-line RAS/BRAF WT or left side setting—bevacizumab + chemotherapy—to branded
and thus premium-priced Vectibix, especially as bevacizumab biosimilars are now widely available and the therapy is
deeply entrenched in the treatment algorithm.

Source:American Society of Clinical Oncology (ASCO) 05/25/2023 (Abstract 3508)
Citeline Analysis 05/26/2023

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Enhertu for Colorectal Cancer (CRC)
Event Date:

05/25/2023

Event Type:

Trial Data - Top-Line Results (Clinical Analysis)

Trial Name:

Phase II - DESTINY-CRC02

Market Group:

Oncology

Lead Company:

Daiichi Sankyo Co., Ltd. (4568)

Partner Companies:

AstraZeneca (AZN)

Former Companies:

N/A

Change to Likelihood of Approval:

5%

Likelihood of Approval:

18% (7% Above Avg.)

Average Approval:

11%

The abstract entitled "Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+)
metastatic colorectal cancer (mCRC): Primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study."
will be presented at ASCO on June 2-6, 2023.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
DesignThis was a multicenter Phase II study. Eligible patients (pts) had centrally confirmed HER2+ (immunohistochemistry [IHC]
3+ or IHC 2+/in situ hybridization [ISH]+) mCRC. Pts with RAS wild-type (wt) or mutant (m) mCRC were eligible. Pts hadreceived prior standard therapy, unless contraindicated; prior anti-HER2 therapy was allowed. In stage 1, 80 pts wererandomized 1:1 to 5.4 (n = 40) or 6.4 (n = 40) mg/kg T-DXd Q3W. In stage 2, an additional 42 pts received 5.4 mg/kg
T-DXd.
Endpoints
Primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR). Secondary
endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
Results
At data cutoff (Nov 1, 2022), most pts in the 5.4 and 6.4 mg/kg T-DXd arms had HER2 IHC 3+ (78.0% and 85.0%), RAS wt
tumors (82.9% and 85.0%), and a median of 3 and 4 prior lines of therapy, respectively. cORR was 37.8% (95% CI,
27.3-49.2%) in the 5.4 mg/kg arm and 27.5% (95% CI, 14.6-43.9%) in the 6.4 mg/kg arm (all partial responses in botharms). Grade ≥3 treatment-emergent adverse events (AEs) were observed in 41/83 pts (49.4%) and 23/39 pts (59.0%) in
the 5.4 and 6.4 mg/kg T-DXd arms, respectively.
Most Common Adverse Events
Serious AEs were observed in 20/83 pts (24.1%) and 12/39 pts (30.8%) in the 5.4 and 6.4 mg/kg arms, respectively.
Independently adjudicated drug-related interstitial lung disease occurred in 7/83 pts (8.4%) with 5.4 mg/kg T-DXd and 5/39

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Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)pts (12.8%) with 6.4 mg/kg T-DXd, and most events were grade 1/2 (1 grade 5 in the 6.4 mg/kg arm).
Conclusion
T-DXd showed promising antitumor activity in pts with HER2+ mCRC at both 5.4 and 6.4 mg/kg doses. Antitumor efficacy
was observed irrespective of RAS mutation status at 5.4 mg/kg T-DXd, and in those with prior anti-HER2 therapy. Overall,safety was consistent with the known safety profile of T-DXd and favored the 5.4 mg/kg dose.

Comment:
HER2-targeted antibody-drug conjugate Enhertu is currently in Phase II trials for second-line and later mCRC. The
drug is also included off-label in the NCCN’s recommendations for RAS/BRAF WT HER2-amplified mCRC in allmetastatic lines of therapy. The NCCN included this recommendation after Enhertu demonstrated impressive
efficacy and reasonable safety in the Phase II DESTINY-CRC01 trial, despite the lack of an official FDA approval.
This early recommendation positioned Enhertu well within this patient population, pending confirmatory resultsfrom the Phase II DESTINY-CRC02 trial. As such, the positive primary results from this latter trial that will bepresented at ASCO 2023, could set the scene for the official entry of Enhertu in the CRC treatment algorithm. Lower
than the ORR from the DESTINY-CRC01, the cORR observed in DESTINY-CRC02 (37.8% in the 5.4mg/kg arm) is still
a positive result for Enhertu, especially as these patients had received a median of 3 prior therapies, but is not very
dissimilar from all the HER2-targeting agents currently vying for a spot within the CRC space. For comparison,Tukysa's ORR from the Phase II MOUNTANEER trial was 38%, with 3.6% CRs (n = 3) and a median DoR of 12.4
months, while results from the HERACLES and MyPathway trials, showed that trastuzumab + Perjeta andtrastuzumab + lapatinib led to ORRs of 32% and 30%, respectively.
The safety and tolerability data, however, highlight a potentially problematic incidence of drug-related interstitial lungdisease (ILD), as well as one yet unspecified grade 5 event. Featuring in Enhertu's blackbox warning for the drug's
approved indications, ILD is a serious side effect which could negatively impact the drug's uptake in CRC, especiallyin a heavily pretreated metastatic population.
Additionally, with RAS/BRAF WT HER2-amplified patients making up less than 5% of the CRC population, and withtrastuzumab (either as Herceptin or biosimilars) and Perjeta also recommended by the NCCN guidelines for off-label
use, and withTukysa recently approved for the same population, Enhertu’s uptake will likely be severely limited in thisindication. Nevertheless, based on these data, we are raising Enhertu's LOA by an additional 5%.

Source:American Society of Clinical Oncology (ASCO) 05/25/2023 (Abstract 3501)
Citeline Analysis 05/26/2023

14

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Tecentriq for Colorectal Cancer (CRC)
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase II - AtezoTRIBE

Market Group:

Oncology

Lead Company:

Roche Holding AG (RHHBY)Bristol Myers Squibb (BMY)

Partner Companies:

Chugai Pharmaceutical (4519)
Ono Pharmaceutical (4528:JP)

Former Companies:

N/A

Change to Likelihood of Approval:

1%

Likelihood of Approval:

35% (9% Below Avg.)

Average Approval:

44%

Comparator

Treatment

Treatment

ITT Population:

ITT Population:

Description

FOLFOXIRI/Bev

FOLFOXIRI/Bev/Atezo

Number of Patients

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Number of Evaluable
Patients

Comparator
pMMR
Population:
FOLFOXIRI/Bev

Treatment

pMMR Population:
FOLFOXIRI/Bev/Atezo

MedianProgression-Free
Survival

11.5 Months

13.1 Months(P=0.15)

11.5 Months

13 Months(P=0.073)(Endpoint=Primary)
mPFS2(Endpoint=Secondary)m2nd PFS(Endpoint=Secondary)15

19.9 Months

5.7 Months

22.6 Months(P=0.164)
6.3 Months(P=0.228)19.9 Months

5.7 Months

21 Months(P=0.269)
6.3 Months(P=0.27)

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)mOS(Endpoint=Secondary)

27.2 Months

33 Months(P=0.136)

26.9 Months

30.8 Months(P=0.172)

The abstract entitled "FOLFOXIRI plus bevacizumab and atezolizumab as upfront treatment of unresectable metastatic
colorectal cancer (mCRC): Updated and overall survival results of the phase II randomized AtezoTRIBE study" will bepresented at ASCO on June 2-6, 2023.
Data from this study were last seen in June 2022.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
DesignThe study had 85% power to detect a HR for PFS (time from randomization to 1st PD or death [PD1]) of .66 in favor of arm
B with 1-sided α error of .10.
Endpoints
Secondary endpoints included PFS2 (time from randomization to PD on any treatment given after PD1 or death [PD2]),
2nd PFS (time from PD1 to PD2), and OS. MMR, TMB, IS IC were correlated to clinical outcome.
Results
218 pts (arm A/B:73/145) were enrolled. Main pts’ characteristics were right-sided 44%/45%, RAS mut
71%/74%, BRAF mut 14%/8%, dMMR 7%/6%, high TMB 10%/12%, high IS IC 32%/32%. At a median follow-up of 37.0
mos, 175 (80%, arm A/B: 64/111) PD1, 150 (69%, arm A/B: 53/97) PD2, and 118 (54%, arm A/B: 43/75) OS events werecollected. Out of 175 pts with a PD1 event, 135 (77%, arm A/B:50/85) received a subsequent treatment; among them, 121
pts (arm A/B: 43/78) had a PD2 event.
In the ITT population, significant interactions between treatment and MMR status (Pint .011), TMB (Pint .008), and IS IC(P int .037) were reported in terms of PFS. Only IS IC was associated with a differential OS benefit (Pint .065), with pts
bearing IS IC-high tumors deriving benefit from adding atezo (HR 0.43, 95%CI 0.19-1.00), differently than those with IS
IC-low tumors (HR 1.09, 95%CI 0.65-1.83). In the pMMR group, significant interactions between treatment and TMB and IS
IC were reported in terms of PFS (Pint .016 and .051, respectively) and OS (Pint .043 and .063, respectively). Pts bearing IS
IC-high tumors derived higher OS benefit from adding atezo (HR 0.44, 95%CI 0.19-1.03), than those with IS IC-low tumors(HR 1.15, 95% CI 0.67-1.97).
Conclusion
Pts with IS IC-high and/or TMB high pMMR mCRC seem to derive a survival benefit from adding atezo to FOLFOXIRI/bev
as upfront treatment. These findings deserve confirmation in a properly designed Phase III trial.

Comment
Combinations of angiogenesis inhibitors and immune checkpoint inhibitors have shown impressive activity in othersolid tumors such as renal cell carcinoma, and the Phase II AtezoTRIBE trial set out to provide evidence of benefit
from adding PD-L1 inhibitor Tecentriq to first-line treatment (chemotherapy and angiogenesis inhibitor bevacizumab)
in patients with newly diagnosed metastatic colorectal cancer. Data from the trial has already shown that Tecentriq
improved the PFS in such patients, with a relatively modest benefit in pMMR patients. Albeit with high P values, theOS update at a median follow-up of 37 months provides further evidence of this benefit, with a median OS of 33
months in the Tecentriq arm (versus 27.2 months in the FOLFOXIRI/bevacizumab arm; P = 0.136) in theintention-to-treat population. In the pMMR population, which represented most of the patients enrolled, the median
OS was 30.8 months in the Tecentriq arm (versus 26.9 months in the comparator arm; P = 0.172).
16

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)OS was 30.8 months in the Tecentriq arm (versus 26.9 months in the comparator arm; P = 0.172).
AtezoTRIBE also employed the use of Oncocyte’s DetermaIO, an immune-related 27-gene expression signature able
to predict benefit from immune checkpoint inhibition in triple-negative breast cancer, and the results from thisanalysis, published in 2022, indicated that the method could be useful in predicting the benefit of adding Tecentriq tochemotherapy (FOLFOXIRI) and bevacizumab through the identification of CRC patients exhibiting certain gene
expression signatures. Additionally, post-hoc subgroup analyses from AtezoTRIBE that will be presented at ASCO
2023 indicate a correlation between tumor mutational burden and Immunoscore IC (Veracyte’s IHC biomarker
measuring CD8 and PD-L1 cell densities and their proximity), with pMMR patients with a high Immunoscore IC result
more likely to derive benefit from the addition of an immune checkpoint inhibitor to chemotherapy and bevacizumab.
Although the pMMR population would be a more lucrative one because of its size, an investigator-led Phase III
COMMIT trial is currently assessing Tecentriq in combination with chemotherapy and bevacizumab in
newly-diagnosed dMMR/MSI-H CRC patients, which represent only 5% of metastatic CRC cases. As such, it remains
to be seen whether Roche, armed with the knowledge gained from AtezoTRIBE, will try to reinforce Tecentriq’s data
in CRC by backing up a bigger and more powered Phase III development programme covering both pMMR anddMMR patients in this indication.

Source:American Society of Clinical Oncology (ASCO) 05/25/2023 (Abstract 3500)
Citeline Analysis 05/26/2023

17

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)DKN-01 for Gastric Cancer
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase IIa - DisTinGuish

Market Group:

Oncology

Lead Company:

Leap Therapeutics, Inc. (LPTX)
BeiGene (BGNE)

Partner Companies:

Eli Lilly (LLY)

Former Companies:

N/A

Change to Likelihood of Approval:

0%Likelihood of Approval:

12% (1% Above Avg.)

Average Approval:

11%

All

Treatment

Treatment

Treatment Description

Number of Patients
Number of Evaluable
Patients

Treatment

DKN-01 +DKN-01 +DKN-01 +Tislelizumab

Tislelizumab

Tislelizumab

+

+

+

Capecitabine

Capecitabine

Capecitabine+ Oxaliplatin+ Oxaliplatin+ Oxaliplatin(PD-L1-Low(PD-L1-High(All Patients)(vCPS < 5)

(vCPS > 5)

Patients)

Patients)

22

N/A

22

19.5 Months

Treatment

Treatment

DKN-01 +DKN-01 +Tislelizumab

Tislelizumab++

Capecitabine

Capecitabine+ Oxaliplatin+ Oxaliplatin(DKK1-High(DKK1-Low

Patients)

Patients)

N/A

N/A

N/A

N/A

N/A

N/A

N/A

18.7 Months

22.0 Months

16.9 Months

24.4 Months

Median Overall
Survival (OS) (Overall
ITT Population)(Endpoint=Secondary)18

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)MedianProgression-Free
Survival (PFS)(Overall ITT

11.3 Months

10.7 Months

11.6 Months

11.3 Months

12.0 Months

73 %

86 %

67 %

90 %

67 %

Population)(Endpoint=Secondary)
Objective Response
Rate (ORR) (Overall
ITT Population)(Endpoint=Primary)
Leap Therapeutics announced the presentation of new long-term follow-up data from Part A of the Phase II DisTinGuishstudy evaluating DKN-01 in combination with BeiGene's tislelizumab and chemotherapy in first-line patients with advanced
gastric or gastroesophageal junction adenocarcinoma (GEA) at the 2023 American Society of Clinical Oncology (ASCO)
Annual Meeting. The abstract entitled "A phase 2 study (DisTinGuish) of DKN-01 in combination with tislelizumab +chemotherapy as first-line (1L) therapy in patients with advanced gastric or GEJ adenocarcinoma (GEA)" will be presented
at the meeting on June 5, 2023.
Data from the study were last seen in November 2022.
Context
Part C is enrolling approximately 160 first-line HER2- GEA cancer patients in a randomized controlled trial of DKN-01 in
combination with tislelizumab and chemotherapy compared to tislelizumab and chemotherapy. The Company anticipatescompleting enrollment in the randomized controlled clinical trial in late 2023 and seeing data from the ongoing colorectal
cancer trial in the coming months.
Per the abstract, further evaluation of biomarkers is also ongoing.
Design
The DisTinGuish study is a Phase II study of DKN-01 in combination with tislelizumab, with or without chemotherapy as
first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being
conducted in three parts in the United States, the Republic of Korea, the United Kingdom, and Germany. Part A enrolled 25
first-line HER2- GEA cancer patients to receive DKN-01 in combination with tislelizumab and capecitabine and oxaliplatin.
Part B enrolled 52 second-line GEA cancer patients whose tumors expressed high levels of DKK1 to receive DKN-01 in
combination with tislelizumab. Tislelizumab is provided for the study through a clinical collaboration with BeiGene.
Per the abstract, this multi-center, single arm Part A of the DisTinGuish study investigated DKN-01 + tislelizumab + CAPOX
as 1L therapy in advanced HER2(-) GEA, regardless of DKK1 and PD-L1 expression levels. Tumor DKK1 and PD-L1 wereassessed by central laboratories.
Endpoints
Per the abstract, the primary endpoint was ORR in a modified intent to treat population (>1 dose DKN-01); secondary
endpoints included PFS and OS in the ITT population.
Results
Findings Part A DisTinGuish
Median overall survival (OS) of 19.5 months and median progression-free survival (PFS) of 11.3 months exceeds
benchmark results in the overall first-line patient population (n=25)
OS and PFS results in all four important biomarker subgroups

19

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)18.7 months OS and 10.7 months PFS in PD-L1-low (vCPS < 5) patients (n=16)
22.0 months OS and 11.6 months PFS in PD-L1-high (vCPS > 5) patients (n=6)
16.9 months OS and 11.3 months PFS in DKK1-high patients (n=12)24.4 months OS and 12.0 months PFS in DKK1-low patients (n=9)
Additional patient with a partial response after 22 months on therapy improves objective response rate (ORR) to
73% in the overall modified intent-to-treat population (n=22), with one (5%) complete response (CR), 15 (68%)
partial responses (PR), 5 (23%) best responses of stable disease (SD), and 1 (5%) non-evaluable (NE)
86% ORR in PD-L1-low patients (n=14: 12 PR, 2 SD)
67% ORR in PD-L1-high patients (n-6: 1 CR, 3 PR, 1 SD, 1 NE)
90% ORR in DKK1-high patients (n=10: 9 PR, 1 NE)
67% ORR in DKK1-low patients (n=9: 1 CR, 5 PR, 3 SD)
Per the abstract, twenty-five patients were enrolled from September 2020 to April 2021. As of January 23, 2023: Medianage was 61 years (22, 80); 17 patients had GEJ adenocarcinoma; 8 had gastric cancer. Twenty-one patients had tumors
with evaluable DKK1 expression. Twenty-two patients had tumors with evaluable PD-L1 expression; the majority (73%)
were low expressors (vCPS <5%). Median (m) duration on treatment is 11.3 months (mo). Seven patients remain on study,
with 4 on-treatment beyond 2 years.
Most Common Adverse Events
Consistent with previous results, combination was well tolerated with manageable toxicity, with most adverse events
related to DKN-01 being low-grade (76%).
Per the abstract, treatment related adverse events (TRAEs) were mild with most G1/2. The most common AEs related tothe study drug regimen were nausea (72%), diarrhea (64%) and fatigue (60%). Five patients experienced G3
DKN-01-TRAEs including decreased neutrophil count (1), diarrhea (1), vomiting (1), hypophosphatemia (2), and pulmonary
embolism (1).
Conclusion
The long-term follow-up data for DKN-01 in combination with tislelizumab and chemotherapy indicates a well-tolerated
treatment with the enhanced response rate, survival, and quality of life for advanced GEA patients. Median overall survival
and progression-free survival for patients treated with DKN-01 plus tislelizumab and chemotherapy exceeded current PD-1
combination benchmarks, especially for those patients with low expression of PD-L1. Together with the previously
reported data on the outcomes with DKN-01 for patients with high DKK1 expression, these results provide support for theongoing randomized controlled clinical trial in first-line GEA patients.

Comment
These data demonstrate the DKN-01 + tislelizumab combination to have an impressive clinical benefit andsubstantially improve survival outcomes in a patient population with poor prognosis. Opdivo is currently the only
targeted therapy for frontline HER2 negative gastric cancer and is the standard of care in combination withchemotherapy. In comparison to the results from the Phase III CheckMate-649 trial, from which Opdivo wasapproved, DKN-01 and tislelizumab combination looks to be a fierce competitor for Bristol Myers Squibb's PD-1
flagship and could potentially dethrone it from its title of standard of care. In CheckMate-649 the median overall
survival was 13.8 months in the intention-to-treat population and the progression-free survival for patients with
PD-L1 CPS ≥ 5 was reported as 7.7 months. In these long-term follow-up data from DisTinGuish, the medianoverall survival was reported as 19.5 months and the progression free survival for patients with PD-L1 CPS ≥ 5 was
11.6 months, both of which look to be markedly higher than those reported in CheckMate-649. Moreover, thesurvival benefit appears to be consistent regardless of DKK1 expression, although the objective response rate is20

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)substantially higher in the DKK1-high subgroup (90% vs 67%), which could potentially warrant the combination
regimen approval without the restriction of DKK1 expression.
Whilst these data poise DKN-01 and tislelizumab to confidently compete with Opdivo, the HER2-negative frontline
market looks set to become increasingly crowded with potential approvals of novel agents zolbetuximab andbemarituzumab, alongside a possible label expansion for Keytruda in combination with Lenvima. In particular,
zolbetuximab has shown impressive Phase III efficacy and safety data in CLDN18.2-positive HER2-negative gastriccancer patients, and also looks set to rivel Opdivo. Investigation into the overlap between DKN-01 overexpression
and CLDN18.2 overexpression could prove useful to discern how directly the DKN-01 + tislelizumab andzolbetuximab regimens will compete and if DKN-01 will be able to carve itself a significant niche. Moreover, mature
data from a double-arm Phase III trial will be crucial to further predict the likely success of DKN-01 and tislelizumab ina market that's set to become progressively competitive. Whilst we await later phase data, we are raising the
likelihood of approval by 3%.

Source:PR Newswire 05/25/2023 (LPTX)
American Society of Clinical Oncology (ASCO) (Abstract 4027, Poster 335)
Citeline Analysis 05/26/2023

21

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Tecentriq for Hepatocellular (Liver) Cancer (HCC) (Including
Secondary Metastases)
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase III - IMbrave050

Market Group:

Oncology

Lead Company:

Roche Holding AG (RHHBY)Bristol Myers Squibb (BMY)

Partner Companies:

Chugai Pharmaceutical (4519)
Ono Pharmaceutical (4528:JP)

Former Companies:

N/A

Change to Likelihood of Approval:

0%Likelihood of Approval:

100% (Same As Avg.)

Average Approval:

100%

The abstract entitled "Efficacy, safety and patient reported outcomes (PROs) from the phase III IMbrave050 trial of
adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients with hepatocellular carcinoma (HCC)at high risk of disease recurrence following resection or ablation" will be presented at the 2023 American Society ofClinical Oncology (ASCO) annual meeting on June 2-6, 2023.
Data from this study were last seen in April 2023.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
DesignIMbrave050 enrolled HCC pts at high risk of recurrence following resection or ablation. Pts were randomized to Arm A(atezo + bev) or Arm B (active surveillance). Pts in Arm A received atezo 1200 mg + bev 15 mg/kg IV q3w for a period of
one year (17 cycles). Pts in Arm B underwent active surveillance for one year and were eligible to crossover to atezo + bev
following independent review facility (IRF) confirmation of recurrence. Pts completed the IL42–EORTC QLQ-C30(reduced) questionnaire at baseline and then at every odd treatment/surveillance visit through Cycle 17.
Endpoints
The primary endpoint was IRF-assessed RFS. Pre-specified exploratory analyses included change from baseline in global
health status (GHS)/quality of life (QoL), physical functioning, role functioning, emotional functioning, and social
functioning. Clinically meaningful deterioration was defined as a ≥ 10-point decrease.
Results
The ITT population included 334 pts in both Arms A and B. With a median follow-up time of 17.4 mo (clinical cutoff date:

22

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)21 Oct 2022), IRF-RFS HR was 0.72 (95% CI: 0.56, 0.93; P = 0.0120). In ITT pts, IL42 completion rates remained ≥ 93%
in both arms from baseline through treatment/surveillance Cycle 17. Mean scores at baseline in both arms were high andsimilar, as measured by the GHS/QoL and physical, role, emotional and social functioning scales. Mean changes frombaseline were not considerable through Cycle 17 and were similar between arms as evidenced by overlapping 95% CIs.
Pts’ GHS/QoL and functioning was maintained through Cycle 17, with no clinically meaningful deterioration observed at
any time.
Most Common Adverse Events
In the safety population, Grade 3 or 4 adverse events occurred in 41% of 332 Arm A pts and 13% of 330 Arm B pts.
Conclusion
Statistically significant and clinically meaningful improvement in RFS was seen in pts receiving atezo + bev vs active
surveillance. Atezo + bev safety was generally manageable, and consistent with the established safety profiles of eachtherapeutic agent and with the underlying disease. PRO outcome analyses revealed similar overall health-related QoL(HRQoL) and functioning between atezo + bev and active surveillance, and that treating high-risk pts with HCC withadjuvant atezo + bev following procedures with curative intent did not result in a clinically meaningful deterioration in
HRQoL or function.

Comment
These first numerical results for Tecentriq in combination with bevacizumab as an adjuvant treatment for high-risk
early-stage HCC are favorable. In topline results released in January this year, Roche announced its flagship HCC
combination had met its primary endpoint of recurrence-free survival (RFS). These updated results for IMbrave050
demonstrate Tecentriq plus bevacizumab reduced the risk of recurrence by 28%. Currently, early-stage HCC
patients are primarily treated with liver transplants or surgical resection, or with locoregional therapies if they are notcandidates for surgery. However, outcomes for these patients are poor, and 70–80% of patients who haveundergone surgery will see their cancer return within five years.
While the efficacy data is a positive step towards providing a treatment option alongside surgery for these high-risk
early-stage patients, the safety data complicates matters. Grade 3 or 4 adverse events occurred in 41% of patients in
the Tecentriq plus bevacizumab arm, which greatly surpasses the 13% grade 3 or 4 adverse event rate in thesurveillance arm.
Although Roche is the first to announce positive results for an immunotherapy in early-stage HCC, Bristol Myers
Squibb is also testing the combination of Opdivo and Yervoy in the adjuvant setting in the Phase III CheckMate 9DX
trial; however, data are not expected until later this year. Despite its head start, it is anticipated the FDA will request
longer-term data from IMbrave050 before granting approval due to the uncertainty around adverse events.
Therefore, monopoly over the currently untouched first-line market will depend on which combination candemonstrated both superior efficacy and safety in this patient population.

Source:American Society of Clinical Oncology (ASCO) (Abstract 4002)
Citeline Analysis

23

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Imjudo for Hepatocellular (Liver) Cancer (HCC) (Including
Secondary Metastases)
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase III - HIMALAYA

Market Group:

Oncology

Lead Company:

AstraZeneca PLC (AZN)
Amgen (AMGN)

Partner Companies:

Bristol Myers Squibb (BMY)
Pfizer (PFE)

Former Companies:

N/A

Change to Likelihood of Approval:

0%Likelihood of Approval:

100% (Same As Avg.)

Average Approval:

100%

The abstract entitled "Outcomes by occurrence of immune-mediated adverse events (imAEs) with tremelimumab (T) plus
durvalumab (D) in the phase 3 HIMALAYA study in unresectable hepatocellular carcinoma (uHCC)" will be presented atthe 2023 American Society of Clinical Oncology (ASCO) annual meeting on June 2, 2023.
Data from this study were last seen in June 2022.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
DesignThis exploratory analysis assessed the association between imAEs and outcomes in HIMALAYA. Safety was assessedin participants (pts) who received ≥1 dose of STRIDE (T 300 mg [one dose] plus D 1500 mg once every 4 weeks [Q4W])
or D (1500 mg Q4W). imAEs were AEs of special interest associated with drug exposure and consistent with an
immune-mediated mechanism of action with no found alternate etiology. Median OS (mOS) and OS rates were estimatedusing the Kaplan–Meier method. OS hazard ratios (HRs) and 95% CIs were calculated using Cox modeling, with imAEs
as a time-varying covariate and stratified by etiology (HBV/HCV/others), ECOG (0/1), and macro-vascular invasion(yes/no) for pts with vs without imAEs of any grade. Pts with >1 imAE were counted once.
Results
In total, 388 pts (STRIDE) and 388 pts (D) were included in the analysis. An improvement in OS was seen with STRIDE in
pts with imAEs vs pts without (HR, 0.73; 95% CI, 0.56–0.95). OS rates at 6, 12, and 24 months (mo) were higher for
STRIDE in pts with imAEs vs pts without. The association between imAEs and OS was less clear for D and may be limitedby small pt number. In a landmark analysis of pts with vs without imAEs within 6 mo of STRIDE (n=307) or D (n=287), OS
HRs (95% CIs) were 0.65 (0.47–0.90) and 1.39 (0.95–2.04), respectively.
24

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)HRs (95% CIs) were 0.65 (0.47–0.90) and 1.39 (0.95–2.04), respectively.
Most Common Adverse Events
Any grade imAEs, Grade 3 or 4 imAEs, and imAEs leading to discontinuation occurred in 139 (35.8%), 49 (12.6%), and22 (5.7%) pts, respectively for STRIDE and 64 (16.5%), 25 (6.4%), and 10 (2.6%) pts, respectively for D. imAEs requiringhigh-dose steroids (≥40 mg prednisone or equivalent daily) occurred in 78 (20.1%) pts for STRIDE and 37 (9.5%) pts for D.
Conclusion
In HIMALAYA, imAEs with STRIDE or D were manageable and generally low grade. In this exploratory analysis, theoccurrence of imAEs was associated with improved OS for STRIDE, generally consistent with findings for other ICIs.

Comment
HCC has notably been a tricky indication for monotherapies to show activity, owing to the aggressive nature of thedisease, so it is often treated with harsher combination therapies. In 2019, Tecentriq plus bevacizumab was the firsttherapy to show remarkable efficacy (42% reduction in the risk of death) over previous standard-of-care Nexavar in
the front-line advanced HCC setting; however, high levels of toxicity are often seen with this combination. Imfinzi incombination with Imjudo, also coined the STRIDE regimen, was the second combination approved in 2022 following
data (22% reduction in the risk of death) that just fell shy of the data seen with Tecentriq + bevacizumab. However,the 57% rate of grade 3 or 4 adverse events seen with the Tecentriq plus bevacizumab combination is inferior to the
26% of grade 3 or 4 adverse events in HIMALAYA.
This exploratory analysis investigating the relationship between immune-mediate adverse events (imAEs) and patient
response to STRIDE suggests overall survival is greater in patients that experience imAEs. As treatment algorithms
have moved on from cytotoxic chemotherapies to more efficacious immunotherapies, a new class of side effects,
termed imAEs have been seen due to the immunologic toxicities related to immunotherapy treatment. In HIMALAYA,
35.8% of patients treated with STRIDE developed any grade imAEs, and grade 3 or 4 imAEs occurred in 12.6% of
patients. The rate of imAEs are substantially greater in patients treated with STRIDE compared to patients treatedwith Imfinzi alone, where only 16.5% of patients developed any grade imAEs and 6.4% were grade 3 or 4.
Interestingly, a higher OS rate was seen at six, 12, and 24 months in patients who developed imAEs than in patients
who didn’t. At 12 months, 69.1% of patients treated with STRIDE that developed imAEs were alive compared to55.2% of patients who did not develop imAEs when treated with STRIDE. Furthermore, the median OS of 23.2
months in the STRIDE imAE arm was far superior to the 14.1-month median OS in the STRIDE no imAE arm.
Therefore, it is hypothesized that both the anti-tumor response and the development of imAEs represent a robust
immune reaction, which could lead to a longer survival time.

Source:American Society of Clinical Oncology (ASCO) (Abstract 4004)
Citeline Analysis

25

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Reblozyl for Myelodysplastic Syndrome (MDS)
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase III - COMMANDS

Market Group:

Oncology

Lead Company:

Merck & Co., Inc. (MRK)Partner Companies:

Bristol Myers Squibb (BMY)
Acceleron Pharma

Former Companies:

CelgeneChange to Likelihood of Approval:

0%Likelihood of Approval:

100% (Same As Avg.)

Average Approval:

100%

Difference Between
Comparator

Treatment

Treatment andComparator

Treatment Description

Epoetin alfa

Reblozyl

Reblozyl vs Epoetin alfa

Number of Patients

176

178

354

Number of Evaluable Patients

154

147

301

31.2 %

58.5 %

51.3 %

74.1 %

29.2 %

47.6 %

46.1 %

66.7 %Red Blood Cell Transfusion Independence(RBC-TI) ≥12 Weeks with Mean Hemoglobin
Increase ≥1.5 g/dL)

N/A(P(Endpoint=Primary)
Hematologic Improvement-erythroid (HI-E) ≥8
Weeks(Endpoint=Secondary)
RBC-TI, 24 Weeks(Endpoint=Secondary)
RBC-TI ≥12 Weeks(Endpoint=Secondary)

26

N/A
(P

N/A
(P=0.0006)
N/A(P=0.0002)

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Bristol Myers Squibb announced first results from the Phase III COMMANDS study of Reblozyl (luspatercept-aamt). Resultsfrom the study will be featured in an abstract entitled "Efficacy and safety results from the COMMANDS trial: A phase 3 study
evaluating luspatercept vs epoetin alfa in erythropoiesis-stimulating agent (ESA)-naive transfusion-dependent (TD) patients(pts) with lower-risk myelodysplastic syndromes (LR-MDS)" at the American Society of Clinical Oncology (ASCO) Annual
Meeting on June 2, 2023 and in an oral presentation entitled "Luspatercept Versus Epoetin Alfa for Treatment (TX) of Anemia in
ESA-naive Lower-risk Myelodysplastic Syndromes (LR-MDS) Patients (Pts) Requiring RBC Transfusions: Data From the Phase 3
COMMANDS Study" at the European Hematology Association (EHA) Congress on June 10, 2023.
Data from the study were last seen in October 2022.
"Efficacy and safety results from the COMMANDS trial: A phase 3 study evaluating luspatercept vs epoetin alfa inerythropoiesis-stimulating agent (ESA)-naive transfusion-dependent (TD) patients (pts) with lower-risk
myelodysplastic syndromes (LR-MDS)" (Abstract 7003)
Context
A supplemental Biologics License Application for Reblozyl is currently under Priority Review with the U.S. Food and Drug
Administration (FDA) for treatment of anemia in ESA-naïve adult patients with very low- to intermediate-risk MDS who may
require RBC transfusions with an assigned Prescription Drug User Fee Act (PDUFA) goal date of August 28, 2023. The
European Medicines Agency has also validated the Type II Variation for Reblozyl in this patient population. Reblozyl isbeing developed and commercialized through a global collaboration with Merck following Merck’s acquisition of Acceleron
Pharma in November 2021.
DesignEligible patients were ≥18 years old with lower-risk MDS who require transfusions. Patients were randomized 1:1 toreceive subcutaneous Reblozyl (starting dose 1.0 mg/kg, titration up to 1.75 mg/kg) once every 3 weeks or epoetin alfa
(starting dose 450 IU/kg, titration up to 1050 IU/kg) weekly for ≥24 weeks.
Per the abstract, eligible pts were ≥ 18 years old with IPSS-R-defined LR-MDS with or without RS, < 5% bone marrowblasts, sEPO levels < 500 U/L, required RBC transfusions (defined as 2–6 RBC units/8 weeks [wk] for ≥ 8 wk
immediately prior to randomization), and were ESA naive.
Endpoints
The primary endpoint evaluated in the COMMANDS study is RBC transfusion independence (RBC-TI) for 12 weeks witha mean hemoglobin increase of ≥1.5 g/dL. Key secondary endpoints include erythroid response (HI-E) of at least 8 weeks
during weeks 1-24 of the study, RBC-TI ≥12 weeks and RBC-TI for 24 weeks.
Results
At the time of the interim analysis, 147 evaluable patients received Reblozyl and 154 evaluable patients received epoetin
alfa, with median treatment durations of 41.6 and 27 weeks, respectively. Results showed 58.5% (n=86) of patients
receiving Reblozyl vs. 31.2% (n=48) of patients receiving epoetin alfa achieved the primary endpoint of RBC-TI of at least
12 weeks with concurrent mean hemoglobin (Hb) increase of at least 1.5 g/dL within the first 24 weeks (p<0.0001). HI-E
increase of at least 8 weeks was achieved by 74.1% (n=109) of Reblozyl patients vs. 51.3% (n=79) of epoetin alfa patients(p<0.0001). Patients treated with Reblozyl achieved more durable responses vs. epoetin alfa, with a median duration of
response of RBC-TI ≥12 weeks (Week 1 to end of treatment) of 126.6 vs. 77 weeks. Within the first 24 weeks oftreatment, RBC-TI of at least 24 weeks was achieved by 47.6% (n=70) ofReblozyl patients vs. 29.2% (n=45) of epoetin alfa
patients (P=0.0006). Benefit with Reblozyl was also observed in clinically relevant subgroups.
Most Common Adverse EventsResults showed a consistent safety profile and no new safety signals.
Per the abstract, treatment-emergent adverse events (TEAEs; any grade) were reported by 164 (92.1%) luspatercept and27

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)150 (85.2%) epoetin alfa pts; 8 (4.5%) and 4 (2.3%) pts discontinued due to TEAEs. Treatment-related AEs were reported
by 54 (30.3%) luspatercept and 31 (17.6%) epoetin alfa pts. AML progression was reported in 4 (2.2%) luspatercept and 5(2.8%) epoetin alfa pts. Overall rates of death were comparable between arms during treatment and post-treatment (32[18.0%] luspatercept, 32 [18.2%] epoetin alfa pts).
Conclusion
Results showed nearly twice as many patients treated with Reblozyl achieved superior transfusion independence withconcurrent hemoglobin increase vs. epoetin alfa, including in clinically relevant subgroups. Reblozyl demonstrated adurable response, with nearly 2.5 years median transfusion independence, 1 year longer than epoetin alfa.
"Luspatercept Versus Epoetin Alfa for Treatment (TX) of Anemia in ESA-naive Lower-risk Myelodysplastic
Syndromes (LR-MDS) Patients (Pts) Requiring RBC Transfusions: Data From the Phase 3 COMMANDS Study"(Abstract S102)
Results
Data to be presented at EHA included both efficacy and safety consistent with results at ASCO, andshowed Reblozyl demonstrated favorable outcomes compared to epoetin alfa across common MDS mutations (SF3B1,
SF3B1a, ASXL1, TET2, DNMT3A, EZH2, IDH2, U2AF1) and had a probability of achieving clinical benefit, regardless ofoverall mutational burden.
Conclusion
Additional results, to be presented during the plenary session at the European Hematology Association Congress, show
Reblozyl demonstrated clinical benefit across patients with spectrum of MDS mutations.

Comment
The release of this ASCO abstract containing data from the Phase III COMMANDS trial demonstrate Reblozyl togreatly improve outcomes for transfusion-dependent lower-risk MDS patients over standard of care epoetin alfa. Inline with the release of topline data late last year, the abstract details the study to have met its primary endpoint of
RBC transfusion independent ≥12 weeks with a concurrent mean hemoglobin increase ≥1.5 g/dL during weeks
1-24. Reblozyl treatment resulted in an absolute improvement of 27.3% compared to epoetin alfa - a highly
significant benefit (p<0.0001). With nearly double the percentage of patients achieving the primary endpoint on
Reblozyl treatment, these results stage an undeniably compelling case for Reblozyl to displace epoetin alfa as thestandard of care treatment.
However, the safety data suggests Reblozyl is more toxic compared to epoetin alfa and potentially less tolerable, withhigher rates of treatment-related adverse events and more patients discontinuing treatment on Reblozyl. One of the
primary treatment goals for low-risk MDS patients is to improve quality of life, and therefore the toxicity profile ofReblozyl has a weighted role in the drug's benefit-risk profile. Nevertheless, the remarkable haematologicalimprovements could arguably outweigh the additional toxicity. Further analysis stratifying the treatment-related
adverse events by grade between the two arms will prove more indicative towards Reblozyl's benefit-risk profile incomparison to epoetin alfa. If the additional treatment-related adverse events consist of higher grade toxicities thenthis could potentially hinder Reblozyl in its bid to become the new standard of care.
Subgroup analysis investigating Reblozyl's affect in non-RS+ and RS+ patients may also be useful to determine if the
drug has utility in an all-comer patient population and to further evaluate its commercial potential. Access to thefront-line setting could prove a lucrative label expansion opportunity for Reblozyl as there are currently limited
treatment options currently available for these patients outside of Erythropoiesis-stimulating agents, yet Reblozyl willneed to demonstrate efficacy regardless of RS status to maximise revenue. For now, we wait to see if further safety
and subgroup analyses will be presented in the oral abstract on June 2nd.
28

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)and subgroup analyses will be presented in the oral abstract on June 2nd.

Source:Business Wire 05/25/2023 (BMY)
American Society of Clinical Oncology (ASCO) (Abstract 7003)
European Hematology Association (EHA) (Abstract S102)
Citeline Analysis

29

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)AB-101 (Artiva) for Non-Hodgkin's Lymphoma (NHL)Event Date:

05/25/2023

Event Type:

Trial Data - Top-Line Results (Clinical Analysis)

Trial Name:

Phase I/II - +/- Rituximab

Market Group:

Oncology

Lead Company:

Artiva Biotherapeutics, Inc.

Partner Companies:

N/A

Former Companies:

N/A

Change to Likelihood of Approval:

1%

Likelihood of Approval:

12% (1% Above Avg.)

Average Approval:

11%

Artiva Biotherapeutics announced the presentation of initial data from the dose-escalation stage of its ongoing Phase I/II
clinical trial of AB-101 in combination with rituximab for the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma(B-NHL) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The abstract entitled "AB-101, an
allogeneic, non–genetically modified, natural killer (NK) cell therapy, evaluated as monotherapy or in combination withrituximab in R/R non-Hodgkin lymphoma" will be presented on June 5, 2023.
DesignThe Phase I/II clinical trial in B-NHL is assessing AB-101 in an outpatient treatment regimen delivered in cycles, with eachcycle consisting of three days of conditioning chemotherapy (250 mg/m 2 or 500 mg/m2 of cyclophosphamide and 30
mg/m 2 of fludarabine) followed by four weekly doses of AB-101 at one billion or four billion cells per dose, each with IL-2
cytokine support. Monotherapy consists of one cycle only, while combination therapy allows for up to four cycles, eachwith two to three doses of rituximab (375 mg/m2).
Patients had received a median of four prior lines of therapy, and 67% were refractory to the prior line of therapy.
Approximately two-thirds have aggressive B-NHL. In the rituximab combination cohort, 89% had been treated with prior
CAR-T therapy. At the time of the data cut, 15 patients in the monotherapy and nine patients in the combination cohorts
were evaluable for assessment of safety.
Results
The Objective Response Rate (ORR) in seven efficacy evaluable patients treated with one billion cells per dose of
AB-101 in combination with rituximab was 57.1% overall, including three Complete Responses (CRs) and one Partial
Response (PR).​ Three of the responses were seen in patients who failed prior CAR-T therapy, and at the time of the datacut, three patients had ongoing responses and were progression free for 5+, 7+ and 9+ months.​
Most Common Adverse Events
AB-101 was well tolerated at one and four billion cells per dose. Up to 16 doses of AB-101 at one billion cells per dosewere administered in combination with rituximab in an outpatient setting. Myelosuppression, consistent with standard

30

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)lymphodepletion regimens, was the most common Grade ≥ 3 toxicity, but was manageable with standard of care. No
prolonged cytopenias were observed. No observations of ICANS / neurotoxicity or GvHD were noted even after 16 doses
per patient.​ Two patients (8%) had Grade 1 reports of CRS, based on low-grade fevers which resolved within five to 24
hours without the usage of steroids and/or tocilizumab.​​ The most common SAEs reported in the monotherapy cohort werefebrile neutropenia (Grade 3+, n=2) and malignant neoplasm progression (Grade 3+, n=2; Grade 1-2, n=1). In the
combination cohort, only one unrelated Grade 3 SAE of pyrexia was noted.​ There were no treatment-related AEs leading
to discontinuation of AB-101.​
Conclusion
Per the abstract, 4 weekly doses of AB-101 given alone or with RTX appeared to be safe and well tolerated without theserious/severe toxicities associated with CAR-T therapies. Preliminary efficacy of the combination treatment isencouraging. The study is ongoing and continues to enroll the combination cohorts and the 4e9 cells/dose level.

Comment
These are encouraging, albeit early results for AB-101, an off-the-shelf enhancer of antibody-dependent cellularcytotoxicity. AB-101 consists of NK cells isolated from cord blood sourced from donors with a high affinity variant of
the receptor CD16 and a KIR-B haplotype. These initial results show good activity in seven heavily pretreatedpatients with a 57% ORR and a 43% CR rate for AB-101 combined with rituximab. Although patients were treated in
the outpatient setting, each 28-day cycle started with three-days of conditioning chemotherapy to deplete
lymphocytes. Patients received four weekly doses of AB-101 each cycle (allogeneic NK cells have a short half-life)
and the trial allowed for up to four cycles. While the conditioning regimen adds to the toxicity, there were notreatment-related adverse events leading to discontinuation of AB-101 and there were no observations of
ICANS/neurotoxicity or graft versus host disease. There was one grade 5 event in the trial (cardiac arrythmia) which
led to a clinical hold that was lifted after determination that it was not related to AB-101. After the clinical hold, theprotocol was amended to exclude patients with a history of significant cardiac disease.
Comparable therapies include Fate Therapeutics FT516, which in 2021 reported a 73% ORR and a 55% CR rate in 11
patients (Fate Therapeutics has since suspended the program as aprt of a large downsizing of the company), andGamida Cell’s GDA-201 which in 2020 reported a 74% ORR and a 68% CR rate in 19 patients. A multicenter Phase
I/II trial expected to enroll 99 patients initiated in 2022 and is evaluating GDA-201 in combination with rituximab. The
expansion phase of the trial will enroll patients with follicular lymphoma and DLBCL.
As we await updated results for AB-101 combined with rituximab, we are raising the LOA by 1%. Also on the horizon,
is initiation of a Phase II trial for Hodgkin’s lymphoma of AB-101 combined with Affimed’s AFM13, an NK cell engager
targeting CD30 and CD16.

Source:Business Wire 05/25/2023 (Artiva Biotherapeutics)
American Society of Clinical Oncology (ASCO) (Abstract 7529)
Citeline Analysis

31

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Talzenna for Prostate Cancer
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase III - TALAPRO-2

Market Group:

Oncology

Lead Company:

Pfizer Inc. (PFE)Partner Companies:

BioMarin (BMRN)

Former Companies:

Medivation

Change to Likelihood of Approval:

0%Likelihood of Approval:

94% (2% Above Avg.)

Average Approval:

92%

PlaceboTreatment

Difference Between
Treatment and Placebo
Talazoparib +Placebo +Talazoparib +Ezalutamide

Ezalutamide

Number of Patients

N/A

N/A

N/A

Number of Evaluable Patients

199

200

399

N/A

13.8

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Treatment Description

Ezalutamide vs Placebo+ Ezalutamide

Radiographic Progression-Free Survival
by BICR(Endpoint=Primary)Radiographic Progression-Free Survival
by BICR - Hazard Ratio
Radiographic Progression-Free Survival
by BICR - Hazard Ratio (BRCA1/2
subgroup)
Radiographic Progression-Free Survival
by BICR - Hazard Ratio (Without
BRCA1/2 Alteration)

32

0.45
(P

0.20
(P

0.68
(P=0.06)

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Overall Survival - Hazard Ratio

Global Health Status/Quality of Life
(GHS/QoL)
Global Health Status/Quality of Life
(GHS/QoL) - Hazard Ratio

N/A

N/A

19.3 %

27.1 %

N/A

N/A

0.69
(P=0.07)

N/A

0.69(P=0.03)

The abstract entitled "TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) +ENZA as first-line (1L) treatment for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboringhomologous recombination repair (HRR) gene alterations" will be presented at the meeting on June 4, 2023.
Data from the study were last seen in February 2023.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
Design
Per the abstract, the researchers report results of the prespecified, independently powered analysis of pts with mCRPC
with HRR gene alterations from Cohorts 1 and 2. From February 2019 to January 2022, 399 pts (169 from Cohort 1)
were randomized 1:1 to receive TALA 0.5 mg or PBO (all received ENZA 160 mg) once daily. Randomization was
stratified by prior abiraterone or docetaxel for castration-sensitive PC (yes vs no). Key eligibility criteria: mildly or
asymptomatic mCRPC with disease progression at study entry, HRR-deficient status prospectively confirmed by tumor
tissue and/or ctDNA testing (genes tested: ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN,PALB2, RAD51C), ECOG PS ≤1, ongoing androgen deprivation therapy, no prior life-prolonging therapy for CRPC.
Endpoints
Per the abstract, primary endpoint: radiographic progression-free survival (rPFS) by BICR per RECIST 1.1 and PCWG3.
Results
Per the abstract, 200 pts received TALA + ENZA and 199 PBO + ENZA. TALA + ENZA significantly improved rPFS by
BICR (HR 0.45; 95% CI, 0.33–0.61; 2-sided P< 0.001; median PFS not reached vs 13.8 months). The HR for rPFS by BICR
was 0.20 (95% CI, 0.11–0.36; P< 0.001) for the BRCA1/2 subgroup (n=155) and 0.68 (95% CI, 0.46–1.02; P = 0.06) inthose without a BRCA1/2 alteration (n=240). The first interim analysis of OS was immature: 21.5% (TALA + ENZA) and26.6% (PBO + ENZA) pts had died; HR 0.69 (95% CI, 0.46–1.03; P = 0.07). TALA + ENZA delayed time to PSA
progression, cytotoxic chemotherapy, and antineoplastic therapy, and improved ORR, PSA response, andinvestigator-assessed PFS2. Time to definitive clinically meaningful deterioration in global health status/quality of life
(GHS/QoL) was significantly longer with TALA + ENZA vs PBO + ENZA (HR 0.69; 95% CI, 0.49–0.97; P = 0.03; median
27.1 vs 19.3 months).
Most Common Adverse Events
Per the abstract, grade (G) 3–4 treatment-emergent adverse events (TEAEs) were reported for 66.2% (TALA + ENZA) vs37.2% (PBO + ENZA). There were more G≥3 hematologic TEAEs (anemia, neutropenia, thrombocytopenia, andleukopenia) with TALA + ENZA vs PBO + ENZA. TEAEs led to discontinuation of TALA in 10.1% vs PBO in 7.0%;
discontinuation rates of ENZA were 7.6% (TALA + ENZA) vs 7.0% (PBO + ENZA).
Conclusion
Per the abstract, TALA + ENZA demonstrated a statistically significant and clinically meaningful improvement in rPFS overstandard of care ENZA as 1L treatment for pts with mCRPC and HRR gene alterations, while delaying time to definitive
clinically meaningful deterioration in GHS/QoL. Toxicity was generally manageable and consistent with known safety
33

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)clinically meaningful deterioration in GHS/QoL. Toxicity was generally manageable and consistent with known safety
profiles of TALA and ENZA.

Comment
Further data for the Talzenna-Xtandi combination in first-line mCRPC all-comers has been widely anticipated after thecontroversy of the Phase III PROpel trial of Lynparza and abiraterone in all-comer mCRPC patients, which recently
ended in the FDA ruling to approve this combination in the restricted BRCA-mutated (BRCAm) population. These
data have focused on the homologous recombination repair (HRR) population, which may be an attempt to solidify
their case for a HRR-approval, in the likely case that the FDA are reluctant to grant an all-comers approval.
Talzenna has shown impressive efficacy in the HRR population, with an HR for rPFS by BICR being 0.20 in the
BRCA1/2 subgroup and 0.68 in those without a BRCA1/2 alteration. No OS data has been presented yet, but after
the controversy of Lynparza in an all-comer population, where it was found in non-HRD patients the OS HR was 1.06,
it is likely the FDA will need detailed OS data across all subgroups for Talzenna and Xtandi in order to grant anapproval.
Lynparza is approved in first-line mCRPC after demonstrating an impressive OS HR of 0.29 in the BRCAm subgroup,
but the BRCA-restricted approval came after an initial fight and subsequent FDA advisory meeting in order to discuss
its efficacy, or lack thereof, in patients without BRCA or homologous recombination repair deficient (HRD) mutations.
Only approximately 20% of prostate cancers are HRD, with an even smaller <10% being BRCAm, severely restricting
AstraZeneca’s initial bid for approval in the total population. This means even if Talzenna fails to gain approval in the
all-comer population, an approval in the larger HRD population over the relatively restricted BRCAm population will
still give it access to a larger population and therefore an advantage over Lynparza.
Competing PARP inhibitor Zejula demonstrated efficacy in both the HRD and BRCAm populations in data released at
ASCO GU 2022, leading to a European approval in April 2023 and an sNDA filing in March 2023. An earlier approvalin Europe, and likely in the US due to early submission of an sNDA, will allow Zejula to gain physician familiarity andhave somewhat of an advantage over Talzenna. Zejula plus abiraterone showed an rPFS of 19.5 months in the
BRCAm subgroup, but Talzenna-Xtandi patients have not yet reached rPFS, with placebo rPFS being 21.9 months.
Talzenna did not reach a median rPFS as of yet, compared to 13.8 months in the comparator subgroup. This makes it
difficult to compare the two in terms of efficacy, as more data is needed. Talzenna will need to demonstrate asignificant efficacy benefit in order to overcome the disadvantage of a later approval and gain an edge over Zejula.

Source:Business Wire 05/25/2023 (PFE)
American Society of Clinical Oncology (ASCO) (Abstract 5004)
Citeline Analysis

34

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Lenvima for Renal Cell Cancer (RCC)
Event Date:

05/25/2023

Event Type:

Trial Data - Updated Results (Clinical Analysis)

Trial Name:

Phase II - w/Pembrolizumab - KEYNOTE-B61

Market Group:

Oncology

Lead Company:

Eisai Co., Ltd. (4523:JP)IQVIA (IQV)
Knight Therapeutics (GUD)

Partner Companies:

Merck (MRK)SFJ Pharmaceuticals

Former Companies:

N/A

Change to Likelihood of Approval:

0%Likelihood of Approval:

100% (Same As Avg.)

Average Approval:

100%

The abstract entitled "First-line lenvatinib + pembrolizumab treatment across non-clear cell renal cell carcinomas: Resultsof the phase 2 KEYNOTE-B61 study" will be presented at ASCO on June 2-6, 2023.
Data from this study were last seen in September 2022.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
DesignAdults with previously untreated advanced non-clear cell RCC and measurable disease per RECIST v1.1 received lenva 20
mg PO QD + pembro 400 mg IV Q6W for up to 18 cycles (~2 y). Histology was assessed by investigator (assessment by
central review is planned).
Endpoints
The primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points
included DOR, DCR, and PFS per RECIST v1.1 by BICR; OS; and safety.
Results
Of 158 treated pts, 93 (59%), 29 (18%), and 21 (13%) had papillary, chromophobe, and unclassified histology,
respectively. Additionally, 6 pts (4%) had translocation and 9 (6%) had other histology. 70 pts (44%) had IMDC favorable
risk and 88 (56%) had intermediate/poor risk. Median follow-up was 14.9 mo (range 8.7-19.7). ORR was 49% (95% CI,
41-57; 9 CRs [6%]; 69 PRs [44%]). DCR was 82% (95% CI, 75-88). Median DOR was not reached (NR; range, 1.5+ to
15.3+ mo). By Kaplan-Meier estimate, 75% of responders had a response for ≥12 mo. For the IMDC favorable risk group,
ORR was 51% (95% CI, 39-64) and DCR was 87% (95% CI, 77-94). For the IMDC intermediate/poor risk group, ORR
was 48% (95% CI, 37-59) and DCR was 78% (95% CI, 68-86). In all pts, median PFS and OS were 17.9 mo (95% CI,

35

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)13.5-NR) and NR (95% CI, NR-NR), respectively; 12-mo rates were 63% and 82%.
Most Common Adverse Events
Treatment-related AEs (TRAEs) occurred in 149 pts (94%) and were consistent with results from other studies. The mostcommon (≥30%) TRAEs were hypertension (n=90; 57%), diarrhea (n=69; 44%), and hypothyroidism (n=58; 37%). Grade
3-4 TRAEs occurred in 81 pts (51%). Overall, 17 pts (11%) discontinued pembro, 14 (9%) discontinued lenva, and 5(3%) discontinued both drugs because of TRAEs. No deaths occurred because of TRAEs.
Conclusion
In pts with advanced non-clear cell RCC enrolled in KEYNOTE-B61, lenva + pembro showed antitumor activity with no newsafety signals. These data support the use of lenva + pembro as first-line treatment for pts with non-clear cell RCC,
regardless of histology.

Comment
Non-clear cell RCC (non-cc RCC) is an understudied area of kidney cancer, with limited options. The combination ofLenvima and Keytruda, although still in earlier phases of investigation, has shed new light into the treatment
algorithm through this undoubtedly positive data and will offer a strong treatment option for physicians, pending anapproval.
The only preferred regimens for a metastatic patient with non-clear cell histology are Cabometyx, Sutent, andentering a clinical trial, as listed by the NCCN, although there are alternative options listed in the ‘otherrecommended regimens’ category. Cabometyx is the standard of care here, despite gaining approval based ontrials primarily investigating clear-cell histology patients. In a meta-analysis, it was found that ORR in
Cabometyx-treated non-cc RCC patients was 27% of patients, PFS was 7 months and OS was 12 months. The mostcommon grade 3 events were skin toxicity (in 4% of patients) and hypertension (in 4% of patients). In a drastic
comparison to these data, the Lenvima and Keytruda combination lead to a median PFS 17.9 months, whilst median
OS was not reached at a median follow up of 14.9 months. Furthermore, the median ORR across all patients was
49%. This data is incredibly positive and given the high area of unmet need for non-cc RCC patients, it is highly likelythat this combination will gain an approval.
Treatment-related adverse events (TRAEs) were higher in the Lenvima-Keytruda doublet, with 51% of patients
experiencing a grade 3 or above TRAE. Although detailed grade 3 and above TRAE data was not disclosed, this lessfavorable safety profile is unlikely to affect physician’s potential prescribing of the doublet due to the sheer size of theunmet need.
Approximately 25% of RCC cases are non-cc, so an approval here will be in a relatively restricted population. Thatsaid, there are limited treatment options for these patients, with those available lacking robust data backing their use
in this patient segment. Lenvima and Keytruda would be able to dominate in this setting relatively unopposed, andprovide a new treatment option for this oft-overlooked patient population. Keytruda and Lenvima are alreadyapproved as a combination regimen in for metastatic ccRCC patients; an additional approval for metastatic non-cc
RCC will give the regimen ubiquity across the metastatic setting.
The Phase II KEYNOTE-B61 study included patients with papillary, chromophobe, translocation, unclassified, and‘other’ histology. Most participants had the papillary histology, which is in line with real-world epidemiology patterns.
The regimen was most effective in patients with the translocation histology, yielding an ORR of 67%, although this is
likely skewed by the small patient population (n=6). The ORR was lowest in patients with chromophobe histology(28% with n=29), but due to lack of other options this is unlikely to curb prescribing of the Lenvima-Keytruda doublet
in these patients, if approved. These results represent a step in the right direction for finding effective therapies for
non-cc RCC patients.
36

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)non-cc RCC patients.

Source:American Society of Clinical Oncology (ASCO) (Abstract 4518)
Citeline Analysis

37

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Cabometyx / Cometriq for Renal Cell Cancer (RCC)
Event Date:

05/25/2023

Event Type:

Trial Data - Top-Line Results (Clinical Analysis)

Trial Name:

Phase II - w/Nivolumab + Ipilimumab - Non-Clear Cell RCC

Market Group:

Oncology

Lead Company:

Exelixis, Inc. (EXEL)
Bristol Myers Squibb (BMY)GSK (GSK)

Partner Companies:

Ipsen (IPSEY)
Swedish Orphan Biovitrum (SOBI)
Takeda Pharmaceutical (TAK)Former Companies:

N/A

Change to Likelihood of Approval:

0%Likelihood of Approval:

100% (Same As Avg.)

Average Approval:

100%

The abstract entitled "Phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal
cell carcinoma with variant histologies (RCCvh)." will be presented at ASCO on June 2-6, 2023.
Data summarized in this event is solely based on data contained in the abstract from the ASCO abstract website. Citeline
was unable to obtain updated data, if any, from the actual presentation at the ASCO conference.
DesignEligible patients (pts) had metastatic RCCvh with ECOG performance status of 0-1 and may have received one line of priortherapy excluding immunotherapy or Cabo. Pts underwent a baseline biopsy and received treatment with Nivo 3 mg/kg
and Ipi 1 mg/kg intravenously Q3 weeks (W) for 4 cycles followed by Nivo 480 mg IV Q4W. Cabo was given continuously atdose of 40 mg daily; reductions to 20 mg daily and 20 mg every other day were allowed.
Endpoints
The primary endpoint was objective response rate (ORR) by RECIST 1.1. Safety was a secondary endpoint.
Results
40 pts have been enrolled. At the time of data cut-off (Dec 9, 2022), 38 pts received at least 1 study drug. 11% (n=4) pts
received prior systemic therapy. 45% (n=17) received all 4 doses of Nivo and Ipi; 18% (n=7) received 3 and 37% (n=14)
received ≤ 2 doses. 61% (n=23) (15 of whom received 4 cycles Nivo/Ipi) received Nivo maintenance (median number ofcycles, 5 (range, 1-21)). 71% (n=27) and 13% (n=5) required Cabo dose reduction to 20 mg and 20 mg every other day,respectively. Median follow-up was 8.4 (range, 2.1-23) months. Objective response was achieved in 8 pts (ORR 21%,
two-sided 80% CI, 13%-32%). Median duration of response was not reached with 5 pts maintaining response > 6months. Median progression-free survival was 8.9 (95% CI, 4.2-12.7) months.

38

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)Most Common Adverse Events
74% (n=28) developed treatment-related grade 3 or higher toxicities; 37% (n=14) developed ≥ grade 3 elevation in AST
or ALT. 29% (n=11) required high dose steroids (prednisone ≥ 40 mg daily or equivalent). 13% (n=5) discontinued all
study drugs due to toxicity. No grade 5 toxicity has been reported.
Conclusion
The study suggests activity for this combination in patients with RCCvh particularly among those without chromophobe
histology. An additional cohort of 20 pts is enrolling with Cabo starting dose of 20 mg daily.

Comment
Non-clear cell RCC (non-cc RCC) is an area of kidney cancer with limited treatment options, having been often
overlooked in clinical trials. The combination of Cabometyx, Opdivo, and Yervoy has shown moderate efficacy inthese patients, although the Phase II trial only enrolled 40 patients. These data are positive, although are not largely
different from currently approved therapies. Furthermore, data released for Lenvima-Keytruda combination therapy
at ASCO 2023 overshadows these data, through more impressive efficacy.
Currently, preferred regimens for a metastatic patient with non-clear cell histology are Cabometyx, Sutent, andentering a clinical trial, as listed by the NCCN. Cabometyx has long reigned as the standard of care here, although its
initial approval was based on trials primarily investigating clear-cell histology patients. In a meta-analysis, it was foundthat ORR in Cabometyx-treated non-cc RCC patients was 27% of patients, PFS was 7 months and OS was 12months. For the triplet combination of Cabometyx-Opdivo-Yervoy, median PFS was 8.9 months, and no OS data wasgiven. Median ORR was 21%; all data is similar to what was seen in Cabometyx-treated patients. Although thisefficacy data is not negative, it is less impressive when compared to the data released for the Lenvima-Keytruda
doublet (PFS: 17.9, ORR: 49%). Non-cc RCC patients do not have many treatment options, and so an approval for
Cabometyx, Opdivo, and Yervoy may be granted to expand these, but it is likely that uptake will be low.
The most common grade 3 events for Cabometyx-treated patients were skin toxicity (in 4% of patients) andhypertension (in 4% of patients). In the Phase II Cabo-Opdivo-Yervoy trial, 74% of patients had a grade 3
treatment-related adverse event. This inflated rate of adverse events does not bode well for the triplet combination,and it is likely that its benefit-risk ratio will not justify its use in patients and lead to low uptake, particularly when
Cabometyx monotherapy is a much more well-tolerated option with similar efficacy.

Source:American Society of Clinical Oncology (ASCO) 05/25/2023 (Abstract 4520)
Citeline Analysis

39

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)List of Biomedtracker ASCO Abstract Night Events
Event

Drug

Date

Lead Company

TickerEvent Type

Trial Name

Link

Bladder Cancer
05/25/2023

Padcev

Astellas Pharma, Inc.

4503:JP

Trial Data - Updated
Results

Phase Ib/II - KEYNOTE-869

482166

FLX475

RAPT Therapeutics, Inc.

RAPT

Trial Data - Updated
Results

Phase I/II - +/-Pembrolizumab

482045

Trial Data - Top-Line
Results

Phase IIb - PREVENT-HF

482162

Cancer
05/25/2023

Chronic Heart Failure - Reduced Ejection Fraction (Chronic HFrEF)
05/26/2023

Coreg

Cheplapharm Arzneimittel
GmbH

Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL
05/25/2023

BGB-11417

BeiGene, Ltd.

BGNE

Trial Data - Updated
Results

Phase I - Mature B-cell Malignancies(China)48217905/25/2023

Breyanzi

Bristol Myers Squibb
Company

BMY

Trial Data - Updated
Results

Phase I/II - TRANSCEND-CLL-004

48203505/25/2023

Venclexta

AbbVie Inc.

ABBV

Trial Data - Top-Line
Results

Phase III - A041702 (w/Ibrutinib +Obinutuzumab; NCI)

482079Colorectal Cancer (CRC)
05/25/2023

Enhertu

Daiichi Sankyo Co., Ltd.

4568

Trial Data - Top-Line
Results

Phase II - DESTINY-CRC02

48208405/25/2023

Tecentriq

Roche Holding AG

RHHBY

Trial Data - Updated
Results

Phase II - AtezoTRIBE

48208505/25/2023

Vectibix

Amgen, Inc.

AMGN

Trial Data - Final
Results

Phase III - PARADIGM

48208605/25/2023

ERAS-007

Erasca, Inc.

ERAS

Trial Data - Top-Line
Results

Phase Ib/II - HERKULES-3 (w/encorafenib+ cetuximab)

482120Shanghai Henlius Biotech
Co. Ltd.

2696

Trial Data - Updated
Results

Phase III - ASTRUM-007

482114BeiGene, Ltd.

BGNE

Trial Data - Updated
Results

Phase II - ROSEWOOD (w/Gazyva)

482031

Leap Therapeutics, Inc.

LPTX

Trial Data - Updated
Results

Phase IIa - DisTinGuish

482053Esophageal Cancer
05/26/2023

HLX10

Follicular Lymphoma (FL)05/25/2023

Brukinsa

Gastric Cancer
05/25/2023

DKN-01

Gastrointestinal Stromal Tumor (GIST)
05/25/2023

Qinlock

Deciphera Pharmaceuticals,
Inc.

DCPH

Trial Data - Updated
Results

Phase III - INTRIGUE

48205005/25/2023

Olverembatinib

Ascentage Pharma Group
Corporation

6855

Trial Data - Updated
Results

Phase I - SJ-0003

48209605/25/2023

THE-630

Theseus Pharmaceuticals,
Inc.

THRX

Trial Data - Top-Line
Results

Phase I/II - THE630-21-101

482138Head and Neck Cancer
05/26/2023

GX-188E

Genexine Inc.

095700

Trial Data - Top-Line
Results

Phase II - w/GX-I7 + Keytruda (Yonsei
University)

48213305/26/2023

Eftilagimod Alpha

Immutep Ltd.

IMMP

Trial Data - Updated
Results

Phase II - TACTI-002 (w/Pembrolizumab)

48210640

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)05/25/2023

PDS0101

PDS Biotechnology
Corporation

PDSB

Trial Data - Updated
Results

Phase II - VERSATILE-002 (US/UK)

48204405/25/2023

CUE-101

Cue Biopharma, Inc.

CUE

Trial Data - Updated
Results

Phase I - First-in-Human (KEYNOTE-A78)

482036

SanofiSNY

Trial Data - Top-Line
Results

Phase I/II - AML/ALL/MDS

482145

Hematologic Cancer
05/26/2023

IPH6101/SAR443579

Hepatocellular (Liver) Cancer (HCC) (Including Secondary Metastases)
05/26/2023

HBM4003

Harbour BioMed

2142

Trial Data - Top-Line
Results

Phase Ib - w/Toripalimab (China)

48213005/25/2023

Imfinzi

AstraZeneca PLC

AZN

Trial Data - Updated
Results

Phase III - HIMALAYA (w/Tremelimumab)

48214205/25/2023

Tislelizumab

BeiGene, Ltd.

BGNE

Trial Data - Updated
Results

Phase III - RATIONALE 301

48203005/25/2023

ImjudoAstraZeneca PLC

AZN

Trial Data - Updated
Results

Phase III - HIMALAYA

48208205/25/2023

AvastinRoche Holding AG

RHHBY

Trial Data - Updated
Results

Phase III - IMbrave050

48208305/25/2023

Tecentriq

Roche Holding AG

RHHBY

Trial Data - Updated
Results

Phase III - IMbrave050

482078

Daiichi Sankyo Co., Ltd.

4568

Trial Data - Top-Line
Results

Phase II - BRE 354

482100482103

HER2+ Breast Cancer
05/25/2023

Patritumab Deruxtecan

HR+/HER2- Breast Cancer
05/25/2023

Pelareorep

Oncolytics Biotech, Inc.

ONC

Trial Data - Top-Line
Results

Phase II - BRACELET-1

05/25/2023

Trodelvy

Gilead Sciences, Inc.

GILD

Trial Data - Final
Results

Phase III - TROPICS-02 (HR+/HER2- MBC) 482081

05/25/2023

OrserduThe Menarini Group

Trial Data Phase III - EMERALD (ER+/HER2-)
Retrospective Analysis

482048Major Depressive Disorder (MDD)
COMP360

COMPASS Pathways

CMPS

Trial Data - Updated
Results

Phase II - Patients w/Cancer

48215305/25/2023

EVX-01

Evaxion Biotech A/S

EVAX

Trial Data - Updated
Results

Phase I/II - NeoPepVac

48212305/25/2023

REGN-3767

Regeneron Pharmaceuticals,
REGN
Inc.

Trial Data - Updated
Results

Phase I - +/- Cemiplimab

482092

05/26/2023
Melanoma

Multiple Myeloma (MM)05/26/2023

TASQ

Active Biotech AB

ACTI

Trial Data - Updated
Results

Phase Ib/IIa - +/- IRd Chemotherapy(University of Pennsylvania)

482111

05/25/2023

REGN5458

Regeneron Pharmaceuticals,
REGN
Inc.

Trial Data - Updated
Results

Phase I/II - LINKER-MM1

482051

Myelodysplastic Syndrome (MDS)
05/25/2023

Reblozyl

Merck & Co., Inc.

MRK

Trial Data - Updated
Results

Phase III - COMMANDS

48205605/25/2023

Imetelstat

Geron Corporation

GERN

Trial Data - Updated
Results

Phase II/III - IMerge(Transfusion-Dependent Subjects)

482039Y-mAbs Therapeutics Inc.

YMAB

Trial Data - Updated
Results

Phase II - 201 (Osteomedullary Disease)482176

Neuroendocrine Tumors (NET)05/26/2023

Danyelza

Non-Hodgkin's Lymphoma (NHL)41

Copyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)05/25/2023

AB-101 (Artiva)

Artiva Biotherapeutics, Inc.

Trial Data - Top-Line
Results

Phase I/II - +/- Rituximab

482026

Non-Small Cell Lung Cancer (NSCLC)
05/25/2023

Reqorsa

Genprex, Inc.

GNPX

Trial Data - Top-Line
Results

Phase I/II - Acclaim-1 - w/Osimertinib

48203705/25/2023

TJ4309TRACON Pharmaceuticals
Inc.

TCON

Trial Data - Updated
Results

Phase Ib/II - +/- Toripalimab (China)

48204305/25/2023

DZD9008

Dizal (Jiangsu)
Pharmaceutical Co., Ltd.

688192

Trial Data - Updated
Results

Phase II - WU-KONG6 (China)

48208805/25/2023

APG-2449

Ascentage Pharma Group
Corporation

6855

Trial Data - Updated
Results

Phase I - XC101 (China)

48208905/25/2023

CAN04

Cantargia AB

CANTA

Trial Data - Top-Line
Results

Phase I/II - CESTAFOUR (EU)48206005/25/2023

LibtayoRegeneron Pharmaceuticals,
REGN
Inc.

Trial Data - Updated
Results

Phase III - EMPOWER-Lung 1 (1st Line)

48206905/25/2023

Datopotamab Deruxtecan

Daiichi Sankyo Co., Ltd.

4568

Trial Data - Updated
Results

Phase Ib - TROPION-Lung02 (w/Keytruda) 482071

Ovarian Cancer
05/25/2023

ZN-c3

Zentalis Pharmaceuticals

ZNTL

Trial Data - Updated
Results

Phase Ib - ZN-c3-002

48205805/25/2023

SL-172154

Shattuck Labs, Inc.

STTK

Trial Data - Final
Results

Phase I - SL03-OHD-101

48205905/25/2023

VS-6766

Verastem, Inc.

VSTM

Trial Data - Updated
Results

Phase II - RAMP 201

482047

Aravive, Inc.

ARAV

Trial Data - Top-Line
Results

Phase Ib/II - w/Gemcitabine andNab-paclitaxel

482022

Pancreatic Cancer
05/25/2023

AVB-500

Prostate Cancer
05/26/2023

MB-105

Mustang Bio Inc.

MBIO

Trial Data - Final
Results

Phase I - City of Hope (NCI)

48216505/25/2023

Talzenna

Pfizer Inc.

PFE

Trial Data - Updated
Results

Phase III - TALAPRO-2

48205505/25/2023

XtandiAstellas Pharma, Inc.

4503:JP

Trial Data - Top-Line
Results

Phase II - ENACT

482076

Renal Cell Cancer (RCC)
05/25/2023

Cabometyx / Cometriq

Exelixis, Inc.

EXEL

Trial Data - Top-Line
Results

Phase II - w/Nivolumab + Ipilimumab Non-Clear Cell RCC

48207405/25/2023

LenvimaEisai Co., Ltd.

4523:JP

Trial Data - Updated
Results

Phase II - w/Pembrolizumab KEYNOTE-B61

48209705/25/2023

Keytruda

Merck & Co., Inc.

MRK

Trial Data - Updated
Results

Phase II - w/Lenvatinib - KEYNOTE-B61

48209805/25/2023

LenvimaEisai Co., Ltd.

4523:JP

Trial Data - Final
Results

Phase III - CLEAR (First Line)

48205405/25/2023

AVB-500

Aravive, Inc.

ARAV

Trial Data - Updated
Results

Phase Ib/II - RCC-003 (US)48202005/26/2023

FyarroAADi Bioscience, Inc.

AADI

Trial Data - Top-Line
Results

Phase Ib/II - w/Pazopanib

48206505/25/2023

Afami-cel

Adaptimmune Therapeutics
plc

ADAP

Trial Data - Updated
Results

Phase II - SPEARHEAD-1

48207205/25/2023

TTI-621

Pfizer Inc.

PFE

Trial Data - Top-Line
Results

Phase I/II - w/Doxorubicin

482062

Noxopharm Limited

NOX

Trial Data - Top-Line
Results

Phase I - IONIC-1 (w/Opdivo)

482108SarcomaSolid Tumors
05/26/2023

42

VeyondaCopyright © 2023 Pharma Intelligence UK Limited (Citeline), a Norstella company (Unauthorized photocopying prohibited)05/26/2023

HLX07

Shanghai Henlius Biotech
Co. Ltd.

2696

Trial Data - Top-Line
Results

Phase Ib/II - w/Chemotherapy (China)

482121

05/26/2023

HLX26

Shanghai Henlius Biotech
Co. Ltd.

2696

Trial Data - Top-Line
Results

Phase I - HLX26-001 (China)

482122

05/26/2023

FORE-8394

Daiichi Sankyo Co., Ltd.

4568

Trial Data - Updated
Results

Phase I/IIa - PLX120-03

48215805/26/2023

FORE-8394

Daiichi Sankyo Co., Ltd.

4568

Trial Data - Updated
Results

Phase I/IIa - PLX120-03

48216305/25/2023

Vitrakvi

Bayer AGBAYN

Trial Data - Top-Line
Results

Phase II - ADVL1823

48214605/25/2023

BAY2416964

Bayer AGBAYN

Trial Data - Updated
Results

Phase I - Safety

48211905/25/2023

Sudocetaxel Zendusortide

Theratechnologies Inc.

THTX

Trial Data - Updated
Results

Phase I - TH1902-CTR-0001

48212405/25/2023

Zotatifin

eFFECTOR Therapeutics, Inc. EFTR

Trial Data - Updated
Results

Phase I/II - Advanced Solid Tumors

48210905/25/2023

Non-Viral TCR Program(ZIOPHARM/Intrexon/NCI)

Alaunos Therapeutics, Inc.

Trial Data - Updated
Results

Phase I/II - Library TCR-T

48210205/25/2023

AU-007

Aulos Bioscience, Inc.

Trial Data - Updated
Results

Phase I/II - First-in-Human

48210405/25/2023

SY-5609

Syros Pharmaceuticals, Inc.

SYRS

Trial Data - Updated
Results

Phase I - SY-5609-101

48209505/25/2023

TPST-1495

Tempest Therapeutics, Inc.

TPST

Trial Data - Top-Line
Results

Phase Ia/Ib - TPST-1495-001(w/Pembrolizumab)

48206405/25/2023

MP0317

Molecular Partners AG

MOLN

Trial Data - Updated
Results

Phase I - First-in-Human (Europe)

48207705/25/2023

CBX-12Cybrexa Therapeutics

Trial Data - Updated
Results

Phase I/II - First-in-Human

48208005/25/2023

Nirogacestat

SpringWorks Therapeutics
Inc.

SWTX

Trial Data - Updated
Results

Phase III - DeFi (Desmoid/Fibromatosis)

48208705/25/2023

CLN-619

Cullinan Oncology, Inc.

CGEM

Trial Data - Top-Line
Results

Phase I - +/- Pembrolizumab

48202805/25/2023

BDC-1001

Bolt Biotherapeutics, Inc.

BOLT

Trial Data - Updated
Results

Phase I/II - BBI-20201001

48202905/25/2023

AFM24

Affimed N.V.

AFMD

Trial Data - Top-Line
Results

Phase I/IIa - Dose Escalation w/ SNK-01

48202405/25/2023

AL102

Ayala Pharmaceuticals, Inc.

ADXS

Trial Data - Updated
Results

Phase II/III - RINGSIDE (Desmoid Tumors) 482025

05/25/2023

PY159

Pionyr Immunotherapeutics,
Inc.

Trial Data - Top-Line
Results

Phase Ia/Ib - w/Pembrolizumab

48203805/25/2023

VT1021

Vigeo Therapeutics, Inc.

Trial Data - Updated
Results

Phase Ib/II - Safety/Pharmacology (01)48204205/25/2023

BGB-A445

BeiGene, Ltd.

Trial Data - Top-Line
Results

Phase I - BGB-A317-A445-101

48203205/25/2023

CTL-002

CatalYm GmbH

Trial Data - Updated
Results

Phase I/IIa - GDFATHER

48203305/25/2023

ATG-008

Bristol Myers Squibb
Company

Trial Data - Updated
Results

Phase I/II - TORCH-2

48205705/25/2023

AFNT-211

Affini-T Therapeutics, Inc.

Trial Data - PreclinicalResults

Preclinical Studies

48204605/25/2023

RLY-4008

Relay Therapeutics, Inc.

Trial Data - Updated
Results

Phase I/II - ReFocus

482049Trial Data - Top-Line
Results

Phase I - First-In-Human (Cornell
University)

482023

Trial Data - Top-Line
Results

Phase Ib/II - MAPLE-1

482101

TCRT

BGNE

BMY

RLAY

Thyroid Cancer
05/25/2023

AIC100AffyImmune Therapeutics,
Inc.

Waldenstrom Macroglobulinemia (WM) / Lymphoplasmacytic Lymphoma (LPL) - NHL
05/25/2023

43

APG-2575

Ascentage Pharma Group
Corporation

6855

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