Oncology News Burst from FDA

November 11, 2022 Oncology News Burst from FDA: FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy >

On November 10, 2022, the Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab (Imfinzi, AstraZeneca Pharmaceuticals) and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

Efficacy was evaluated in POSEIDON (NCT03164616), a randomized (1:1:1), multicenter, active-controlled, open-label study in patients with metastatic NSCLC who had not received prior systemic treatment. Patients were randomized to one of three treatment arms: (1) tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks. Patients were treated with a fifth tremelimumab dose at week 16; (2) durvalumab plus platinum-based chemotherapy for 4 cycles followed by durvalumab and maintenance chemotherapy; or (3) platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy.

Treatment was continued until disease progression or unacceptable toxicity. This approval is based on a comparison of treatment arm 1 and 3 (675 patients).

The major efficacy outcome measures were progression-free survival (PFS) assessed using blinded independent central review according to RECIST v1.1. and overall survival (OS). Tremelimumab plus durvalumab and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared to platinum-based chemotherapy (hazard ratio [HR] of 0.77 [95% CI: 0.65, 0.92], 2-sided p-value = 0.00304); median OS was 14 months (95% CI: 11.7, 16.1) and 11.7 months (95% CI: 10.5, 13.1) in the treatment arm 1 and 3, respectively. Median PFS was 6.2 months (95% CI: 5.0, 6.5) and 4.8 months (95% CI 4.6, 5.8) in the treatment arms, respectively (HR 0.72 [95% CI: 0.60, 0.86], 2-sided p-value = 0.00031).

Overall response rate was 39% (95% CI: 34,44) in and 24% (95% CI: 20, 29) in the treatment arm 1 and 3, respectively. Median duration of response was 9.5 months (95% CI: 7.2, not reached) and 5.1 months (95% CI: 4.4, 6.0) in the two treatment arms.

The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities (≥ 10%) were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia, and thrombocytopenia.

The recommended tremelimumab dose for patients weighing 30 kg or more is 75 mg IV every 3 weeks with durvalumab 1500 mg IV and platinum-based chemotherapy for 4 cycles, then durvalumab 1500 mg with maintenance chemotherapy every 4 weeks. A fifth tremelimumab dose (75 mg) should be given at week 16.

Using the above schedule, for patients weighing 30 kg or less, the recommended tremelimumab dose is 1 mg/kg and the durvalumab dose is 20 mg/kg.

View full prescribing information for Imjudo and Imfinzi.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncology


November 10, 2022 Oncology News Burst from FDA: FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer >

On November 8, 2022, the Food and Drug Administration approved cemiplimab-rwlc (Libtayo, Regeneron Pharmaceuticals, Inc.) in combination with platinum-based chemotherapy for adult patients with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK, or ROS1 aberrations.

Efficacy was evaluated in Study 16113 (NCT03409614), a randomized, multicenter, multinational, double-blind, active-controlled trial in 466 patients with advanced NSCLC who had not received prior systemic treatment. Patients were randomized (2:1) to either cemiplimab-rwlc plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by cemiplimab-rwlc and maintenance chemotherapy or placebo plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by placebo and maintenance chemotherapy.

The main efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) as assessed by blinded independent central review (BICR).

Cemiplimab-rwlc plus platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared to placebo plus chemotherapy (hazard ratio [HR] of 0.71 [95% CI: 0.53, 0.93], two-sided p-value = 0.0140). Median OS was 21.9 months (95% CI: 15.5, not evaluable) in the cemiplimab-rwlc plus chemotherapy arm and 13.0 months (95% CI: 11.9, 16.1) in the placebo plus chemotherapy arm. Median PFS per BICR was 8.2 months (95% CI: 6.4, 9.3) in the cemiplimab-rwlc plus chemotherapy arm and 5.0 months (95% CI: 4.3, 6.2) in the placebo plus chemotherapy arm (HR 0.56; 95% CI: 0.44, 0.70, p<0.0001). Confirmed ORR per BICR was 43% (95% CI: 38, 49) and 23% (95% CI: 16, 30) in the respective treatments.

The most common (≥15%) adverse reactions were alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite.

The recommended cemiplimab-rwlc dose is 350 mg IV every 3 weeks. Refer to the prescribing information for the agents administered in combination with cemiplimab-rwlc for recommended dosing information, as appropriate.

View full prescribing information for Libtayo

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncology


October 26, 2022 Oncology News Burst from FDA: FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma >


On October 25, 2022, the Food and Drug Administration granted accelerated approval to teclistamab-cqyv (Tecvayli, Janssen Biotech, Inc.), the first bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Teclistamab-cqyv was evaluated in MajesTEC-1 (NCT03145181; NCT04557098), a single-arm, multi-cohort, open-label, multi-center study. The efficacy population consisted of 110 patients who had previously received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and had not received prior BCMA-targeted therapy.

The main efficacy outcome measure was overall response rate (ORR) as determined by the Independent Review Committee assessment using International Myeloma Working Group 2016 criteria. ORR was 61.8% (95% CI: 52.1, 70.9). With a median follow-up of 7.4 months among responders, the estimated duration of response (DOR) rate was 90.6% (95% CI: 80.3%, 95.7%) at 6 months and 66.5% (95% CI: 38.8%, 83.9%) at 9 months.

The prescribing information for teclistamab-cqyv has a Boxed Warning for life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Among patients who received teclistamab-cqyv at the recommended dose, CRS occurred in 72% of patients, neurologic toxicity in 57%, and ICANS in 6%. Grade 3 CRS occurred in 0.6% of patients and Grade 3 or 4 neurologic toxicity occurred in 2.4%.

Because of the risks of CRS and neurologic toxicity, including ICANS, teclistamab-cqyv is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli REMS.

The most common adverse reactions (≥20%) occurring in the 165 patients in the safety population, were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

The recommended teclistamab-cqyv dose is 0.06 mg/kg via subcutaneous injection on Day 1, 0.3 mg/kg on Day 4, and 1.5 mg/kg on Day 7, followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity.

View full prescribing information for Tecvayli.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic. The application reviews may be ongoing at the other regulatory agencies.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. The application also was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncology


October 25, 2022 Oncology News Burst from FDA: FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma >

On October 21, 2022, the Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma (uHCC).

Efficacy was evaluated in HIMALAYA (NCT03298451), a randomized (1:1:1), open-label, multicenter study in patients with confirmed uHCC who had not received prior systemic treatment for HCC. Patients were randomized to one of three arms: tremelimumab 300 mg as a one-time single intravenous (IV) infusion plus durvalumab 1500 mg IV on the same day, followed by durvalumab 1500 mg IV every 4 weeks; durvalumab 1500 mg IV every 4 weeks; or sorafenib 400 mg orally twice daily until disease progression or unacceptable toxicity. This approval is based on a comparison of the 782 patients randomized to tremelimumab plus durvalumab to sorafenib.

The major efficacy outcome was overall survival (OS). Tremelimumab plus durvalumab demonstrated a statistically significant and clinically meaningful improvement in OS compared to sorafenib (stratified hazard ratio [HR] of 0.78 [95% CI: 0.66, 0.92], 2-sided p value = 0.0035); median OS was 16.4 months (95% CI: 14.2, 19.6) versus 13.8 months (95% CI: 12.3, 16.1). Additional efficacy outcomes included investigator-assessed progression-free survival (PFS) and overall response rate (ORR) according to RECIST v1.1. Median PFS was 3.8 months (95% CI: 3.7, 5.3) and 4.1 months (95% CI: 3.7, 5.5) for the tremelimumab plus durvalumab and sorafenib arms, respectively (stratified HR 0.90; 95% CI: 0.77, 1.05). ORR was 20.1% (95% CI: 16.3, 24.4) in the tremelimumab plus durvalumab arm and 5.1% (95% CI: 3.2, 7.8) for those treated with sorafenib.

The most common (≥20%) adverse reactions occurring in patients were rash, diarrhea, fatigue, pruritis, musculoskeletal pain and abdominal pain.

The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg IV as a single dose in combination with durvalumab 1500 mg at Cycle 1/Day 1, followed by durvalumab 1500 mg IV every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg IV as a single dose in combination with durvalumab 20 mg/kg IV, followed by durvalumab 20 mg/kg IV every 4 weeks.

View full prescribing information for Imjudo.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Tremelimumab was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncology


September 8, 2022 Oncology News Burst from FDA: durvalumab approved for locally advanced or metastatic biliary tract cancer >

On September 2, 2022, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca UK Limited) in combination with gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancer (BTC).

Efficacy was evaluated in TOPAZ-1 (NCT03875235), a randomized, double-blind, placebo-controlled, multiregional trial that enrolled 685 patients with histologically confirmed locally advanced unresectable or metastatic BTC who had not previously received systemic therapy for advanced disease.

Trial demographics were as follows: 56% Asian, 37% White, 2% Black, and 4% other race; 7% Hispanic or Latino; 50% male and 50% female; median age was 64 years (range 20-85) and 47% were 65 years or older. Fifty-six percent had intrahepatic cholangiocarcinoma, 25% had gallbladder cancer, and 19% had extrahepatic cholangiocarcinoma.

Patients were randomized 1:1 to receive:

  • durvalumab 1,500 mg on Day 1+ gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle up to 8 cycles, followed by durvalumab 1,500 mg every 4 weeks, or
  • placebo on Day 1+ gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle up to 8 cycles, followed by placebo every 4 weeks.

Durvalumab or placebo were continued until disease progression or unacceptable toxicity. Treatment was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit, as determined by the investigator.

The major efficacy outcome measure was overall survival (OS). Tumor assessments were conducted every 6 weeks for the first 24 weeks, then every 8 weeks until confirmed objective disease progression. A statistically significant improvement in OS was demonstrated in patients randomized to receive durvalumab with gemcitabine and cisplatin compared to those randomized to receive placebo with gemcitabine and cisplatin. Median OS was 12.8 months (95% CI: 11.1, 14) and 11.5 months (95% CI: 10.1, 12.5) in the durvalumab and placebo arms, respectively (hazard ratio 0.80; 95% CI: 0.66, 0.97, p=0.021). The median progression-free survival was 7.2 months (95% CI: 6.7, 7.4) and 5.7 months (95% CI: 5.6, 6.7) in the durvalumab and placebo arms, respectively. Investigator-assessed overall response rate was 27% (95% CI: 22% - 32%) and 19% (95% CI: 15%-23%) in the durvalumab and placebo arms, respectively.

The most common (≥20%) adverse reactions occurring in patients were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.

The recommended durvalumab dose is 1,500 mg every 3 weeks for patients with a body weight ≥30 kg when given with gemcitabine and cisplatin, followed by 1,500 mg every 4 weeks as a single agent until disease progression or unacceptable toxicity. For patients with a body weight <30 kg, the recommended dose is 20 mg/kg every 3 weeks with gemcitabine and cisplatin followed by 20 mg/kg every 4 weeks until disease progression or unacceptable toxicity.

View full prescribing information for Imfinzi.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, Singapore’s Health Sciences Authority (HSA), and Switzerland’s Swissmedic. The application reviews may be ongoing at the other regulatory agencies.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. The application also was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncology


July 27, 2022 Oncology News Burst from FDA: pembrolizumab >

On March 4, 2022, the Food and Drug Administration approved nivolumab (Opdivo, Bristol-Myers Squibb Company) with platinum-doublet chemotherapy for adult patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting.

This represents the first FDA approval for neoadjuvant therapy for early-stage NSCLC.

Efficacy was evaluated in CHECKMATE-816 (NCT02998528), a randomized, open label trial in patients with resectable, histologically confirmed Stage IB (≥4 cm), II, or IIIA NSCLC (AJCC/UICC staging criteria) and measurable disease (RECIST v1.1.). Patients were enrolled regardless of the tumor PD-L1 status. A total of 358 patients were randomized to receive either nivolumab plus platinum-doublet chemotherapy administered every 3 weeks for up to 3 cycles, or platinum-chemotherapy alone administered on the same schedule.

The main efficacy outcome measures were event-free survival (EFS) and pathologic complete response (pCR) by blinded independent central review. Median EFS was 31.6 months (95% CI: 30.2, not reached) in the nivolumab plus chemotherapy arm and 20.8 months (95% CI: 14.0, 26.7) for those receiving chemotherapy alone. The hazard ratio was 0.63 (97.38% CI: 0.43, 0.91; p=0.0052). The pCR rate was 24% (95% CI: 18.0, 31.0) in the nivolumab plus chemotherapy arm and 2.2% (95% CI: 0.6, 5.6) in the chemotherapy alone arm.

The most common adverse reactions (incidence ≥20%) occurring in patients were nausea, constipation, fatigue, decreased appetite, and rash. The addition of nivolumab to chemotherapy did not result in more frequent delays or cancellations of surgery. The median lengths of hospital stays following definitive surgery and the rates of adverse reactions identified as surgical complications were similar for patients in both arms of the trial.

The recommended nivolumab dose is 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for 3 cycles.

View full prescribing information for Opdivo.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews may be ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application five months ahead of the FDA goal date.

This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer.