FDA News

FDA approves Opdivo-Yervoy combination for subset of patients with metastatic colorectal cancer

The FDA granted accelerated approval to the combination of nivolumab and low-dose ipilimumab for treatment of microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer, according to the agents’ manufacturer.

The approval applies to adults aged 12 and older whose disease progressed after treatment with fluoropyrimidine, oxaliplatin or irinotecan chemotherapy.

The combination of nivolumab (Opdivo, Bristol-Myers Squibb) 3 mg/kg and low-dose ipilimumab (Yervoy, Bristol-Myers Squibb) — administered as 1-mg/kg injections — is the first immuno-oncology (I-O) combination approved for these patients.

“Bristol-Myers Squibb is pleased to bring forward Opdivo plus Yervoy as the first I-O/I-O combination therapy to be approved in this type of colorectal cancer,” Ian M. Waxman, MD, development lead for gastrointestinal cancers at Bristol-Myers Squibb, said in a company-issued press release. “Our commitment to studying Opdivo plus Yervoy, which target distinct but complementary immune pathways, results from our strong belief that rational combinations in biomarker-selected populations may improve clinical benefit for patients.”

The FDA based the approval on results of the ongoing phase 2 CheckMate -142 trial, which included 119 patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer who received at least one prior line of therapy for metastatic disease.

Independent radiographic review committee assessment showed nearly half (46%; 95% CI, 35-58) of the 82 patients who had undergone prior treatment with fluoropyrimidine-, oxaliplatin- or irinotecan-based chemotherapy responded to treatment with nivolumab plus ipilimumab. Of these, three patients (3.7%) achieved complete response and 35 (43%) achieved partial response.

Median duration of response had not been reached (range, 1.9-23.2+), but 89% of responses lasted at least 6 months, and 21% lasted at least 12 months.

In the overall study population, 58 patients (49%) responded to treatment; of these, five (4.2%) achieved complete response and 53 (45%) achieved partial response. Median duration had not been reached (range, 1.9-23.2+). The majority (83%) had responses of 6 months or longer, and 19% had responses that lasted at least 12 months.

The most common adverse reactions reported among patients treated with the combination included fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%) and vomiting (20%).

Nearly half (47%) of patients in CheckMate -142 experienced serious adverse reactions. The most common included colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia and dehydration.

The recommended dosing schedule calls for 3 mg/kg nivolumab to be administered via IV infusion, followed by 1 mg/kg ipilimumab administered as IV infusion on the same day. This treatment is administered every 3 weeks for four doses.

Patients then receive nivolumab maintenance therapy, which consists of 240 mg via IV infusion every 2 weeks until disease progression or unacceptable toxicity.

“Metastatic colorectal cancers with [mismatch repair-deficient] or [microsatellite instability-high] biomarkers can be difficult to treat, and some patients may need additional options,” Heinz-Josef Lenz, MD, FACP, L. Terrence Lanni chair in gastrointestinal cancer research at Keck School of Medicine of University of Southern California and principal investigator of CheckMate -142 at USC Norris Comprehensive Cancer Center, said in the release. “The FDA’s approval of an I-O/I-O combination provides us with an encouraging approach to address this challenging disease in patients who have progressed following treatment with three standard chemotherapy options.”

The nivolumab-ipilimumab combination also is approved for previously untreated patients with intermediate- or poor-risk advanced renal cell carcinoma, as well as for patients with unresectable or metastatic melanoma.

The FDA granted accelerated approval to the combination of nivolumab and low-dose ipilimumab for treatment of microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer, according to the agents’ manufacturer.

The approval applies to adults aged 12 and older whose disease progressed after treatment with fluoropyrimidine, oxaliplatin or irinotecan chemotherapy.

The combination of nivolumab (Opdivo, Bristol-Myers Squibb) 3 mg/kg and low-dose ipilimumab (Yervoy, Bristol-Myers Squibb) — administered as 1-mg/kg injections — is the first immuno-oncology (I-O) combination approved for these patients.

“Bristol-Myers Squibb is pleased to bring forward Opdivo plus Yervoy as the first I-O/I-O combination therapy to be approved in this type of colorectal cancer,” Ian M. Waxman, MD, development lead for gastrointestinal cancers at Bristol-Myers Squibb, said in a company-issued press release. “Our commitment to studying Opdivo plus Yervoy, which target distinct but complementary immune pathways, results from our strong belief that rational combinations in biomarker-selected populations may improve clinical benefit for patients.”

The FDA based the approval on results of the ongoing phase 2 CheckMate -142 trial, which included 119 patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer who received at least one prior line of therapy for metastatic disease.

Independent radiographic review committee assessment showed nearly half (46%; 95% CI, 35-58) of the 82 patients who had undergone prior treatment with fluoropyrimidine-, oxaliplatin- or irinotecan-based chemotherapy responded to treatment with nivolumab plus ipilimumab. Of these, three patients (3.7%) achieved complete response and 35 (43%) achieved partial response.

Median duration of response had not been reached (range, 1.9-23.2+), but 89% of responses lasted at least 6 months, and 21% lasted at least 12 months.

In the overall study population, 58 patients (49%) responded to treatment; of these, five (4.2%) achieved complete response and 53 (45%) achieved partial response. Median duration had not been reached (range, 1.9-23.2+). The majority (83%) had responses of 6 months or longer, and 19% had responses that lasted at least 12 months.

The most common adverse reactions reported among patients treated with the combination included fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%) and vomiting (20%).

Nearly half (47%) of patients in CheckMate -142 experienced serious adverse reactions. The most common included colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia and dehydration.

The recommended dosing schedule calls for 3 mg/kg nivolumab to be administered via IV infusion, followed by 1 mg/kg ipilimumab administered as IV infusion on the same day. This treatment is administered every 3 weeks for four doses.

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Patients then receive nivolumab maintenance therapy, which consists of 240 mg via IV infusion every 2 weeks until disease progression or unacceptable toxicity.

“Metastatic colorectal cancers with [mismatch repair-deficient] or [microsatellite instability-high] biomarkers can be difficult to treat, and some patients may need additional options,” Heinz-Josef Lenz, MD, FACP, L. Terrence Lanni chair in gastrointestinal cancer research at Keck School of Medicine of University of Southern California and principal investigator of CheckMate -142 at USC Norris Comprehensive Cancer Center, said in the release. “The FDA’s approval of an I-O/I-O combination provides us with an encouraging approach to address this challenging disease in patients who have progressed following treatment with three standard chemotherapy options.”

The nivolumab-ipilimumab combination also is approved for previously untreated patients with intermediate- or poor-risk advanced renal cell carcinoma, as well as for patients with unresectable or metastatic melanoma.

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