Exelixis (EXEL) Announces Consistent Efficacy Benefits Across Subgroups of Phase 3 CheckMate -9ER Trial of CABOMETYX in Combination with OPDIVO as First-line Treatment for Patients with Advanced RCC

June 4, 2021 9:01 AM EDT

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Exelixis, Inc. (NASDAQ: EXEL) today announced results from a post-hoc exploratory analysis demonstrating that the efficacy benefits seen in the phase 3 CheckMate -9ER trial with CABOMETYX® (cabozantinib) in combination with Bristol Myers Squibb’s OPDIVO® (nivolumab) compared with sunitinib as a first-line treatment for advanced renal cell carcinoma (RCC) were observed across analyzed subgroups, including those based on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk status, site of metastases and extent of tumor burden at baseline. The data will be presented as part of the Poster Session: Genitourinary Cancer – Kidney and Bladder at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held virtually, June 4-8, 2021. All posters will be available on demand beginning at 6:00 a.m. PT on Friday, June 4.

“To inform treatment decisions, we are eager to gain a deeper understanding of how baseline disease characteristics may impact clinical outcomes for patients treated with cabozantinib in combination with nivolumab, and this analysis supports that the combination regimen may be an appropriate option in the first-line setting for a wide range of patients with renal cell carcinoma,” said Andrea Apolo, M.D., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, who served on the study’s steering committee. “Some of the baseline characteristics, including the presence of bone metastases, are associated with worse outcomes, making it encouraging to see that the combination regimen demonstrated efficacy benefits in these patients.”

As presented at the ASCO 2021 Genitourinary Cancers Symposium (ASCO GU) in February 2021, at a median follow-up of 23.5 months in the CheckMate -9ER intent-to-treat population, median progression-free survival (PFS) was doubled at 17.0 months for CABOMETYX in combination with OPDIVO compared with 8.3 months for sunitinib (hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.43-0.64; P<0.0001). Median overall survival (OS) was not yet reached for the combination regimen versus 29.5 months with sunitinib (HR 0.66; 95% CI: 0.50-0.87; P=0.0034). Objective response rate (ORR) was 54.8% with CABOMETYX in combination with OPDIVO versus 28.4% with sunitinib, and complete response (CR) rate was 9.3% versus 4.3%, respectively.

In this new exploratory analysis presented at ASCO 2021 (abstract #4553), patient subgroups were pre-specified based on the following baseline characteristics: IMDC risk status (favorable-, intermediate- or poor-risk disease), site of metastases (liver, bone or lung), number of organ sites with tumor lesions (one or at least two) and size of tumor lesions (less than or greater than/equal to the median). Across subgroups, median PFS was longer and ORR rates were consistently higher for patients treated with CABOMETYX in combination with OPDIVO compared with sunitinib. CR rates were higher with CABOMETYX in combination with OPDIVO versus sunitinib in most subgroups, ranging up to 16.3% for CABOMETYX in combination with OPDIVO versus 8.4% for sunitinib in the subgroup with a lower than median tumor lesion size, and 19.7% for CABOMETYX in combination with OPDIVO versus 4.4% for sunitinib in the subgroup where metastatic spread was limited to one organ site. See table below for additional details.

“Following the FDA approval of CABOMETYX in combination with OPDIVO as a first-line treatment for advanced renal cell carcinoma in January, these data further underscore the combination regimen’s role as an important option for a broad range of patients in need of first-line treatment for RCC,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “Our goal is to provide this combination regimen to as many eligible patients as possible, and we’re glad to see these data support its use across RCC patients regardless of prognosis.”

Median OS was not yet reached for CABOMETYX in combination with OPDIVO in any subgroup, but 15-month OS rates were higher with CABOMETYX in combination with OPDIVO compared with sunitinib in all subgroups. Hazard ratios favored CABOMETYX in combination with OPDIVO compared with sunitinib for most subgroups (see table). Note, the trial was not powered to assess efficacy in subgroups. For certain subgroups, particularly patients with favorable risk, few events were observed in either arm.

Table

Subgroup

Median PFS (95% CI),
months

ORR, %

CR, %

HR for OS
(95% CI)

C+N*

SUN**

C+N

SUN

C+N

SUN

IMDC favorable risk (n=146)

24.7
(13.1–NEα)

12.8
(9.6–18.5)

66.2
(54.3–76.8)

44.4
(32.7–56.6)

9.5

9.7

0.94
(0.46-1.92)

IMDC intermediate risk (n=376)

17.5
(11.3–19.4)

8.5
(7.0–9.8)

55.9
(48.4–63.1)

28.7
(22.4–35.8)

10.6

3.2

0.74
(0.50-1.08)

IMDC poor risk (n=129)

9.9
(5.9–17.7)

4.2
(2.9–5.6)

37.7
(25.6–51.0)

10.3
(4.2–20.1)

4.9

1.5

0.45
(0.27-0.76)

Liver metastases (n=127)

10.9
(7.0-15.2)

5.6
(2.8-8.2)

49.3
(37.4-61.3)

20.4
(10.6–33.5)

1.4

1.9

0.47
(0.27–0.82)

Bone metastases

(n=151)

18.2
(8.3-20.1)

4.4
(3.7-7.0)

48.1
(36.7-59.6)

11.1
(4.9-20.7)

6.3

0.0

0.64
(0.39-1.06)

Lung metastases (n=491)

16.8
(11.9-19.4)

8.2
(6.9-9.6)

55.8
(49.3-62.2)

29.5
(23.9-35.5)

7.5

4.4

0.63
(0.46-0.86)

One organ site with tumor lesions

(n=129)

24.9
(13.1-NE)

12.6
(8.2-19.2)

62.3
(49.0-74.4)

35.3
(24.1-47.8)

19.7

4.4

0.79
(0.33-1.90)

Two or more organ sites with tumor lesions

(n=519)

15.3
(11.2-19.3)

7.1
(5.9-9.2)

53.3
(47.0-59.4)

26.7
(21.4-32.6)

6.9

4.3

0.63
(0.47-0.84)

Tumor lesion size less than the median (72.1 mm) (n=327)

20.3
(17.7-24.9)

9.8
(8.3-12.4)

61.9
(53.9-69.4)

35.9
(28.7-43.7)

16.3

8.4

0.64
(0.38-1.06)

Tumor lesion size greater than or equal to the median (72.1 mm) (n=324)

11.1
(9.0-15.6)

6.3
(5.4-8.3)

47.9
(40.0–55.8)

20.5
(14.5–27.6)

2.5

0.0

0.64
(0.46-0.89)

*C+N: CABOMETYX (cabozantinib) in combination with OPDIVO (nivolumab)

**SUN: sunitinib

αNot estimable

In CheckMate -9ER, CABOMETYX in combination with OPDIVO was generally well tolerated and reflected the known safety profiles of the tyrosine kinase inhibitor and immunotherapy components in previously untreated advanced RCC. The most common adverse reactions reported in at least 20% of patients treated with CABOMETYX in combination with OPDIVO were diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough and upper respiratory tract infection. A safety analysis with extended follow-up reported at ASCO GU this year identified no new safety signals; among patients treated with OPDIVO and CABOMETYX, 6.6% discontinued both agents due to treatment-related adverse events, 9.7% discontinued OPDIVO only, and 7.2% discontinued CABOMETYX only.

About CheckMate -9ER

CheckMate -9ER is an open-label, randomized (1:1), multi-national phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma with a clear cell component. A total of 651 patients (22% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to CABOMETYX at a dose of 40 mg QD and OPDIVO (n = 323) versus sunitinib (n = 328). The primary endpoint is PFS. Secondary endpoints include OS and ORR. The primary efficacy analysis compares the doublet combination regimen of CABOMETYX and OPDIVO versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.



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