Summer Inventory Overview Of the approvals of FDA drugs and programs in the field of solid tumors from June to August

The summer is coming to an end, it's hot, and the approval of drug programs in the field of solid tumors is also extremely hot

On June 22, 2022, the FDA accelerated approval of dalafenib in combination with trimetinib for the treatment of patients with non-resectable or metastatic solid tumors with BRAF V600E mutations in adults or children ≥6 years of age

The accelerated approval is based on a number of studies such as BRF117019, NCI-MATCH, CTMT212X2101, COMBI-d, COMBI-v and BRF113928, among which the BRF117019 study was conducted for patients with multiple solid tumors such as BRAF V600E mutant high-grade glioma (HGG), biliary tract cancer, low-grade glioma (LGG), small bowel adenoma, gastrointestinal stromal tumor and anaplastic thyroid cancer (ATC).

Adverse reactions that occur ≥ 20% in adults include fever, fatigue, nausea, rash, chills, headache, bleeding, cough, vomiting, constipation, diarrhea, myalgia, arthralgia, and edema, and adverse reactions that occur ≥ 20% in pediatric patients include fever, rash, vomiting, fatigue, dry skin, cough, diarrhea, acne-like dermatitis, headache, abdominal pain, nausea, bleeding, constipation, and paronychia

The recommended dose of darafenib for adult patients is 150 mg, oral, bid; Trametinib 2 mg orally, qd

On July 14, 2022, the FDA approved zotinib for the treatment of unresectable, recurrent, or refractory ALK-positive IMT patients who are adults or children ≥1 years of age

The approval is based on two multicenter, single-arm, open-label clinical trials, ADVL0912 in 14 pediatric patients and A8081013 in
7 adults.

The study was enrolled in unresectable, relapsed, or refractory ALK-positive IMT patients with the primary study endpoint of ORR
.

The results showed that for 14 pediatric patients, the patient ORR was 86%; For 7 adult patients, the patient ORR was 71.
4%.

Adverse reactions that occur ≥ 35% of pediatric patients are vomiting, nausea, diarrhea, abdominal pain, rash, visual impairment, upper respiratory tract infections, cough, fever, musculoskeletal pain, fatigue, edema, constipation, and headache
.

Adverse reactions that occur ≥ 35% of adult patients are visual impairment, nausea, and edema
.

The recommended dose of clozotinib in adult patients is 250 mg orally, bid until the disease progresses or toxicity becomes intolerable
.

The recommended dose of crizotinib in pediatric patients is 280 mg/m² orally, bid until disease progression or toxicity is intolerable
.

On August 5, 2022, the FDA approved T-Dxd for the treatment of unresectable or metastatic HER2 hypoexpression adult breast cancer who had previously been treated for metastatic disease or had a recurrence
of the disease during/after completion of adjuvant therapy.

The approval is based on the DESTINY-Breast04 study, a randomized, multicenter, open-label trial of 557 patients with unresectable or metastatic HER2 low-expression breast cancer, of which HER2 low expression is defined as IHC 1+ or IHC 2+/ISH-
as measured in the central laboratory.

The trial included two cohorts of 494 hormone receptor-positive (HR+) patients and 63 hormone receptor-negative (HR-) patients
.

Patients were randomly assigned (2:1) to receive T-Dxd 5.
4 mg/kg, q3w (n=373) or chemotherapy of choice (n=184, including elibulin, capecitabine, gemcitabine, albumin paclitaxel, or paclitaxel).

The primary study endpoint was progression-free survival (PFS) in HR+ patients assessed by the Blinded Independent Center Review Committee (BICR) based on RECIST v1.
1, and the secondary study endpoints were PFS in the population as a whole (all HR+ and HR-patients), overall survival (OS) in HR+ patients, and OS
from the population as a whole.

The median age of patients was 57 years, and 24% of patients were ≥ 65 years.


In the HR+ cohort, the median PFS in the T-Dxd and chemotherapy groups was 10.
1 months and 5.
4 months, respectively (HR=0.
51, p<0.
0001).


In the overall population, the median PFS in the T-Dxd group and the chemotherapy group was 9.
9 months and 5.
1 months , respectively (HR = 0.
50, p<0.
0001).

In the HR+ cohort, the median OS in the T-Dxd and chemotherapy groups were 23.
9 months and 17.
5 months, respectively (HR=0.
64, p=0.
0028).


In the overall population, the median OS in the T-Dxd and chemotherapy groups was 23.
4 months and 16.
8 months, respectively (HR=0.
64, p=0.
001).

In the T-Dxd group, adverse reactions ≥ 20% of patients were nausea, fatigue, alopecia, vomiting, anemia, constipation, decreased appetite, diarrhea, and musculoskeletal pain
.

Prescription information includes black-box warnings
for interstitial lung disease and embryo-fetal toxicity.

The recommended dose of T-Dxd is 5.
4 mg/kg, q3w until disease progression or toxicity becomes intolerable
.

On August 5, 2022, the FDA approved d'altamide tablets in combination with docetaxel for the treatment of adult mHSPC patients
.

The approval is based on the ARASENS study, a randomized, multicenter, double-blind, placebo-controlled trial
that included 1306 patients with mHSPC.

Patients were randomly assigned to receive oral dalotamide 600 mg, bid plus up to 6 cycles of docetaxel 75 mg/m², q3w, or placebo plus docetaxel
.

All patients received gonadotropin-releasing hormone analogues or bilateral orchiectomy
.

The primary study endpoint was OS and the time to pain progression (TTPP) was the additional exploration endpoint
.

The median age of patients was 67 years, and 17% of patients were ≥ 75 years
.

The disease stage was M1a (disease spread to distant lymph nodes) in 3% of patients, M1b (spread to bones) in 83% of patients, and M1c (spread to organs)
in 14% of patients.

The results showed that the median OS of the dalotamide-docetaxel group and the placebo-plus docetaxel group were not reached and 48.
9 months (HR=0.
68, p<0.
0001), respectively, and there was also a statistical difference in TTPP between the two groups (HR=0.
79, unilateral p=0.
006).

Adverse reactions that occurred in patients with a prevalence of ≥ 10% and more than 2% higher than in the placebo-plus docetaxel group included constipation, decreased appetite, rash, bleeding, weight gain, and hypertension
.

Abnormalities that occur ≥ 30% of laboratory tests include anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, elevated aspartate aminotransferase (AST), elevated alanine transaminases (ALT), and hypocalcemia
.

The recommended dose of darotamide is 600 mg orally, bid, and taken with food until the disease progresses or the toxicity becomes intolerable
.

The recommended dose of docetaxel is 75 mg/m², intravenous infusion, q3w, up to 6 cycles
.

The first dose of docetaxel should be applied
within 6 weeks after the start of dalotamide therapy.

On August 10, 2022, the FDA approved capmatinib for the treatment of adult patients
with METASTN 14-jump mutant NSCLC.

Capmatinib received accelerated approval for the same indication on May 6, 2020, accelerating approval of the GEOTTRY mono-1 trial based on a multicenter, non-randomized, open-label, multi-cohort study, based on data from an additional 63 patients in the study, plus an additional 22 months of follow-up time
.

The study included 160 patients with MET exon 14-jump mutant metastatic NSCLC who received capmatinib 400 mg orally, bid until disease progression or toxicity was intolerable
.

The primary study endpoint was ORR and duration of remission (DOR)
for BICR assessment.

The median age of patients was 71 years, and 16% of patients had central nervous system metastases
.

Of the 100 patients who had previously been treated, 81% received first-line treatment, 16% received second-line treatment, and 3% received third-line treatment
.

For 60 patients who had not previously received treatment, the ORR was 68% and the median DOR was 16.
6 months
.

For 100 patients who had previously been treated, the ORR was 44% and the median DOR was 9.
7 months
.

Adverse reactions that occur ≥ 20% of patients are edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased
appetite.

The recommended dose of Capmatinib is 400 mg orally, bid, with or without meals
.

On August 11, 2022, the FDA accelerated approval of T-Dxd for the treatment of adult patients
with HER2 mutant incision or metastatic NSCLC who had previously received systemic therapy.

It is the first drug
approved to treat herr2-mutant NSCLC.

T-Dxd was assessed at 6.
4 mg/kg (n=152) in multiple trials and 5.
4 mg/kg (n=102) in randomized dose exploration trials
.

Response was consistent across dose levels, but investigators observed an increased incidence of interstitial lung disease/pneumonia at higher doses
.

Therefore, the recommended dose of T-Dxd is 5.
4 mg/kg, q3w
.

The accelerated approval is based on the DESTINY-Lung02 study, a multicentre, multi-cohort, randomized, blinded, dose-optimized trial
.

Studies included patients with non-squamous NSCLC with non-resectable or metastatic HER2 mutations who had disease progression
after previous systemic therapy.

Based on the HER2 mutation in the patient's tumor specimen, the researchers selected the patient for T-Dxd treatment
.

Patients receive T-Dxd 5.
4 mg/kg, q3w until disease progression or toxicity becomes intolerable
.

The main efficacy analysis population of the study included 52 patients, with a median age of 58 years (range: 30-78) and 69% of patients were female
.

The primary study endpoints were ORRs and DORs
assessed by BICR according to the RECEST v1.
1 criteria.

The results showed that the patients had an ORR of 58% and a median DOR of 8.
7 months
.

Including laboratory abnormalities, adverse reactions that occur ≥ 20% include nausea, decreased white blood cell count, decreased hemoglobin, decreased neutrophil count, decreased lymphocyte count, decreased platelet count, decreased albumin, elevated ALT, elevated AST, fatigue, constipation, decreased appetite, vomiting, increased alkaline phosphatase, and hair
loss.

Prescription information includes black-box warnings
for interstitial lung disease and embryo-fetal toxicity.

References:

1.
       Traveller

Reviewer: Mia

Typography: Wanderer

Execution: Traveller

END