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ASCO Goes Virtual 2020

American Society of Clinical Oncology(ASCO)is an organization which represents around 45,000 physicians of all oncology sub-specialities. It was founded in the year 1964. ASCO works extensively towards conquering cancer through its educational programmes, in-depth research, and patient care of utmost quality.

ASCO organises an annual platform for the news release and discussion of scientific events regarding latest advancements in the cancer treatment and its care, for oncologists, industry leaders,major media houses worldwide.The various cancer treatments covered are targeted therapy, radiation therapy, surgery, chemotherapy, stem cell transplant, hormone therapy and immunotherapy.

#ASCO Goes Virtual 2020annual meeting major drug developers shared the performance of the numerous drugs in various therapy fields like immunotherapy, chemotherapy, radiation therapy from ongoing or already completed trials.

 Immuno-Oncology

The definition of immunotherapy is the use of the body’s natural defences (immune system) to fight disease. Immuno-Oncology is a type of immunotherapy that is specifically targeted to fight cancer.

Immuno-oncology works by stimulating our immune system to fight back, when it wouldn’t usually be able to.

Normally, our immune system is able to destroy cancer cells in our body, however sometimes cancer cells can adapt and mutate, effectively hiding from our immune system. This is when tumours can develop and become a threat to our health. Immuno-oncology involves mobilising lymphocytes to recognise and eliminate cancer cells using the body’s immune system.

In theory, this is already much better for patients than the current treatments for cancer, which are principally surgery, chemotherapy and radiation.

Immuno-oncology allows cancer cells to be targeted, leaving the rest of the body unharmed. It also has far fewer limitations, being applicable to tumours at all stages of the disease with much higher efficiency and durability (meaning fewer recurrences!).  Since the first immuno-oncology treatment was approved in 2010, it has proven effective in treating melanoma and lymphoma, as well as lung, kidney and bladder cancer.

Following are some of the advancements and results of major clinical trials grouped by indications covered in #ASCO Goes Virtual 2020:

 1. Lung Cancer

Lung cancer starts in lung and can spread to other parts of the body. It almost always starts in the spongy, pinkish gray walls of the lungs’ airways (called bronchi or bronchioles) or air sacs (called alveoli).

Lung cancer has the highest mortality worldwide which accounts for 19% of all cancer deaths and is classified into 2 types: NSCLC and SCLC.

1.1 Non Small cell Lung Cancer(NSCLC)

NSCLC majorly develops in the inner lining of alveoli, bronchioles, or bronchi and covers almost 85% of the total lung cancer cases.

NSCLC witnessed some breakthrough therapies even before the start of ASCO 2020 namely Checkmate-227 and Checkmate-9LA which has been approved concurrently and is all set to have a combined effect in their uptake curve.

Clinical Trials –

In the tables mentioned below, are shown the results published for some of the key I-O trials

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
KN-189
(1L NSQ)
Keytruda + Chemo31.022.0
HR 0.56
9.0
HR 0.49
48.3%
CR 0.5%
IMPower150*
(1L NSQ)
Tecentriq + Chemo~2019.2
HR 0.78
8.3
HR 0.62
63.5%
CR: 3.7%
IMPower110**
(1L PD-L1 High)
Tecentriq Mono15.720.2
HR 0.59
8.1
HR 0.63
38.3%
CITYSCAPE
(1L PD-L1≥1)
Tecentriq + Tira
(anti-TIGIT)
10.9-5.5
HR 0.58
37%
CM-227
(1L PD-L1≥1)
Opdivo + Yervoy43.117.1
HR 0.79
5.1***
HR 0.81
36.4%
CM-9LA
(1L AC)
Opdivo + Yervoy + Chemo12.7****15.6
HR 0.66
6.8
HR 0.70
38%

Table 1.1 NSCLC Metastatic Key I-O Trials

* 2year PFS Data

+ Preliminary Median O.S. as mentioned in Mirati 1Q’20 Earnings report

1 ASCO presentation is on exploratory data on brain metastases

2 ASCO presentation is on exploratory data on Patient-reported outcomes (PROs)

3 Minimum follow-up

KN-189 and IMPower150 both focus on 1L NSQ. KN-189’s trial performance is robust as it provides patients great OS and PFS benefit by almost doubling it. According to the trials results it has been recommended for utilising in 1L NSQ treatment.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
KN-799
(Cohort A*)
(Stage 3 Unresec)
Keytruda + Chemo8.36 mo: 87.2%
HR -
6 mo: 81.4%
HR -
67%
CR 2.7%
KN-799
(Cohort B#) (Stage 3 Unresec)
Keytruda + Chemo5.86 mo: 94.8%
HR -
6 mo: 85.2%
HR -
56.6%
CR 3.8%
PACIFIC
(Stage 3 Unresec)
Imfinzi + Chemo33.336 mo: 57%
HR 0.69
16.8
HR 0.52
-

Table 1.2 NSCLC Early Stage Key I-O Trials

* Cohort A: Pembrolizumab 200mg on Day 1 with paclitaxel 200 mg/m2 + carboplatin AUC 6 Q3W for cycle 1, then paclitaxel 45 mg/m2 + carboplatin AUC 2 QW for cycles 2–3 for 6 weeks in conjunction with standard thoracic radiotherapy (60 Gray [Gy]) followed by 14 cycles of pembrolizumab 200mg  Q3W

# Cohort B: Pembrolizumab 200mg on Day 1 with cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W (nonsquamous only) in cycles 1–3 in conjunction with standard thoracic radiotherapy (60 Gray [Gy]) followed by 14 cycles of pembrolizumab 200mg  Q3W

1: PACIFIC ASCO Presentation is on immune-mediated adverse events

Landmark O.S./P.F.S mentioned wherever median is not reached

PACIFIC, KN-799(A), and KN-799(B) focus on stage-III NSCLC. KN-799 showed significant antitumor activity in both the cohorts. PACIFIC has first mover advantage in this setting, which is complemented with the consistent data published.

1.2 Small Cell Lung Cancer (SCLC)

SCLC covers almost 15% of all the lung cancer cases. Though this type of lung cancer is less common but it is much more aggressive as compared to NSCLC. It metastasises quickly and easily thus facilitating its spread to different organs of the body

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
KN-604
(1L ED)
Keytruda + EP21.610.8
HR 0.8
4.5*
HR 0.75
71%
CASPIAN
(1L ED)
Imfinzi + EP25.112.9
HR 0.75
5.1
HR 0.80
67.9%
CASPIAN
(1L ED)
Imfinzi + Treme + EP25.110.4
HR 0.82
4.9
HR 0.84
58.4%

Table 1.3 SCLC Metastatic Stage Key I-O Trials

*mPFS is based on IA2 (median follow-up 13.5mo), rest information is based on FA

All the 3 clinical trials focus on 1L ED. Results show that Keytruda+EP in the trial KN-604 achieved significant improvement in the mPFS of patients treated with the combination. Although the mOS increased but the combination could not achieve the pre-specified endpoint.

CASPIAN result trials show that there was significant improvement in the mOS of the patients administered with Imfinzi+EP, but the same cannot be said for the patients administered with Imfinzi+EP+Treme combination although the ORR is significant. Safety in both the experimental arms was in line with the existing safety profiles.

2. Renal Cell Carcinoma (RCC)

Renal cell carcinoma is the most common type of kidney cancer in adults. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma, renal cell adenocarcinoma, and renal cell cancer.

Clinical trial data on RCC released on ASCO platform offers open discussion of benefits from trial data and approved drug benefits are shown below.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
KN-426
(1L AC)
Keytruda + Inlyta2724 Mo: 74%
HR 0.68
15.4
HR 0.71
60%
CR: 9%
KN-146
(2L+ Post PD-L1)
Keytruda + Lenvima-NR
HR -
11.7
HR -
51%

Table 2.1 RCC Metastatic Stage Key I-O Trials

Keynote-426 is a phase 3 trial for RCC withKeytruda+Inlyta which has not reached its median OS but shows promising results when looked into the median PFS and ORR data. KN-146 too has an impressive data in the post IO settings

3. Melanoma

Melanoma is a serious form of skin cancer results from uncontrolled growth of skin pigment cells. It can be more serious than the other forms of skin cancer because of a tendency to spread to other parts of the body (metastasize) and cause serious illness and mortality.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
COLUMBUS
(1L mMEL MT)
Encorafenib + Binimetinib60.633.6
HR 0.62
14.9
HR 0.52
-

Table 3.1 Metastatic Melanoma Key I-O Trials

COLUMBUS published its 5 years follow up data in BRAF Mutant Type segment but cannot surpass the efficacy of Checkmate 067 in the mutant type segment

Trial Name
(Indication)
RegimenFollow-up
(mo)
mRFS
(mo)
KN-054
(Adj. AC)
Keytruda Mono>36@36 mo: 64%*
HR 0.56
KN-054
(Adj. MT)
Keytruda Mono>36@36 mo: 62%*
HR 0.51
KN-054
(Adj. WT)
Keytruda Mono>36@36 mo: 62%*
HR 0.66
KN-054
(Adj. PD-L1 +ve)
Keytruda Mono>36@36 mo: 65%*
HR 0.57
KN-054
(Adj. PD-L1 -ve)
Keytruda Mono>36@36 mo: 57%*
HR 0.45
KN-054
(Adj. MT)
Keytruda Mono>36@36 mo: 62%*
HR 0.51
COMBI-AD
(Adj MT)
Dabra+Trame6060 mo: 52%
HR

Table 3.2 Early Stage Melanoma Key I-O Trials

* RFS

Mentioned as 5 years: ~60 mos

@ 3.05  years

COMBI-AD published strong 5 years follow up data in BRAF Mutant type segment which says more than 50% of the patient on the drug has not recurred yet. 3 years follow up data for KN-054 also has not yet reached the median RFS in any of its segments. These studies will be beneficial for patients in Adj melanoma setting.

4. Hepatocellular Carcinoma (HCC)

HCCis a cancer which affects the liver. This predominantly occurs in the patients who are already suffering with some type of liver disease and/or livercirrhosis. Obesity, hypertension, type-II diabetes are some of the major risk factors which lead to development of NASH are leading factors for HCC development in US.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
KN-524*
(1L HCC)
Keytruda + Lenvima10.622
HR -
8.6
HR -
36%
CR: 1%

Table 4.1 HCC Metastatic Stage Key I-O Trials

Merck’s KN-524 focuses on 1L HCCwith Keytruda+Lenvima.

Keytruda+Lenvima combination regimen shows promising antitumor activity and yields clinically significant objective response rates. Although the risk of adverse events is also higherit is said to be tolerable, which is a matter of some concern.

Dr. Jonathan Cheng, VP, Oncology Clinical Research, Merck expressed that the tumor response rates with combination regimen emphasizes its potential.

Many physicians have a positive reaction towards the results generated by the combination regimen, but some are concerned with the toxicity levels as well. This trial competes with Roche’s Tecentriq + Avastin (IMBrave 150) which got approved in the same setting on 29th of May’2020.

5. Colorectal Carcinoma (CRC)

CRC is the cancer which affects the colon or the rectum of a person, can also be named accordingly based on where the cancer starts.People’s changing lifestyle leading to obesity, less or no exercise, unhealthy food and drink consumption habits, tobacco consumption are some of the leading factors supporting the growth of CRC.

CRC starts as abnormal growth structures in the innermost lining of the rectum or colon. These growth structures are called polyps and they can be precancerous in nature or they could be caused due toinflammatory response which are quite common.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
KN-177
(1L CRC MSI-h)
Keytruda Mono28.4-16.5
HR 0.60
43.8%
CR: 11%

Table 5.1 CRC Metastatic Stage Key I-O Trials

With only half of the data available for Merck & Co’s Keynote-177 study of Keytruda it seems premature to say the results will change clinical practice. Yet this is what researchers are claiming in a late-breaking ASCO presentation that hails Keytruda as a new standard of care in first-line MSI-high/MMRd colorectal cancer.

6. Bladder Cancer

Bladder cancer starts when cells that make up the urinary bladder start to grow out of control.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
IMvigor 010
(Adj.)
Tecentriq Mono21.9NR
HR 0.85
19.4#
HR 0.89
Javelin 100
(1L Maint. AC)
Avelumab + BSC19.621.4
HR 0.69
NR
HR 0.62
Javelin 100
(1LMaint.PD-L1+ve)
Avelumab + BSC19.6NR
HR 0.56
NR
HR 0.56

Table 6.1 Bladder Metastatic Stage Key I-O Trials

Javelin Bladder is coming up with an impressive data in AC and PD-L1 +ve segments and may acquire a good market share.

7. Gastric Cancer

Gastric cancer is the sixth most common cancer and the third most common cause of cancer-related death in the world.  Although rates are low in North America and Northern Europe—in the United States, stomach malignancy is currently the 15th most common cancer.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
KN-061
(2L)
Keytruda Mono24.09.1
HR 0.81
1.5
HR 1.25
16.3%

Table 7.1 Gastric Metastatic Stage Key I-O Trials

The data doesn’t looks strong as compared to the I-O approval in 3L setting.

8. Mesothelioma

Mesothelioma is a cancer which develops due to exposure to asbestos. It mainly develops in the innermost linings of lungs but can also start its development in walls ofabdomen,heart, or other organs as well. It is anaggressive cancer and its occurrence is rare.People who are prone to inhale asbestos are liable to develop this type of cancer.

Trial Name
(Indication)
RegimenFollow-up
(mo)
mOS
(mo)
mPFS
(mo)
ORR
(%)
PrE0505
(1L Meso Unresec)
Imfinzi + Chemo20.621.1
HR -
--

Table 8.1 Mesothelioma Metastatic Stage Key I-O

Although the median OS is very promising, there are other competitors venturing into the market.

References

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