Drug Trials Snapshot: AVMAPKI FAKZYNJA CO-PACK
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the AVMAPKI FAKZYNJA CO-PACK Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
AVMAPKI FAKZYNJA CO-PACK (avutometinib; defactinib)
ave-MAP-kee Fak-zin-jah co-pac
Verastem Inc.
Original Approval date: April 28, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
AVMAPKI FAKZYNJA CO-PACK, a combination of avutometinib and defactinib, each kinase inhibitors, is indicated for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy.
How is this drug used?
AVMAPKI is administered as capsules taken by mouth two times a week (Day 1 and Day 4) with food for the first three weeks of each 4-week cycle.
FAKZYNJA is administered as a tablet taken by mouth two times a day with food for the first three weeks of each 4-week cycle.
Who participated in the clinical trials?
The FDA approved AVMAPKI FAKZYNJA CO-PACK based on evidence from one clinical trial (RAMP-201/NCT04625270) using efficacy and safety data from 57 patients with KRAS-mutated recurrent LGSOC. The trial was conducted in seven countries including Belgium, Canada, France, Italy, Spain, the United Kingdom, and the United States. Of the 57 patients, 28 were enrolled at sites in the United States. Pooled safety data from two trials (RAMP-201; FRAME/NCT03875820), including 136 patients with recurrent LGSOC, also supported safety evaluation of AVMAPKI FAKZYNJA CO-PACK.
How were the trials designed?
The benefits and side effects of AVMAPKI FAKZYNJA CO-PACK were evaluated in one clinical trial using data from 57 patients with KRAS-mutated recurrent LGSOC.
The RAMP-201 trial is an open-label, multicenter study. Patients received AVMAPKI 3.2 mg orally twice weekly for the first three weeks out of a 4-week cycle and FAKZYNJA 200 mg orally twice daily for the first three weeks out of a 4-week cycle until disease progression or unacceptable toxicity.
The major efficacy outcome measure was overall response rate (ORR) assessed by blinded independent review committee) according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. An additional efficacy outcome measure was duration of response (DoR). Tumor response assessments occurred every 8 weeks for the first 72 weeks and every 12 weeks thereafter.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarize the percentage of patients by sex enrolled in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of patients by ethnicity in the clinical trial used to evaluate the safety and efficacy of AVMAPKI FAKZYNJA CO-PACK.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics
| Demographic | All Patients N=57 n (%) |
|---|---|
| Sex | |
| Female | 57 (100) |
| Age, years | |
| Mean (SD) | 60 (12) |
| Median (min, max) | 60 (29, 87) |
| Age group, years | |
| 18 to <65 | 34 (60) |
| ≥65 | 23 (40) |
| Race | |
| White | 43 (75) |
| Black or African American | 2 (4) |
| Asian | 2 (4) |
| Not reported | 10 (18) |
| Ethnicity | |
| Hispanic or Latino | 2 (4) |
| Not Hispanic or Latino | 43 (75) |
| Not reported | 11 (19) |
| Unknown | 1 (2) |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
In the RAMP-201 trial, 44% of patients with previously treated KRAS-mutated LGSOC experienced complete or partial shrinkage of their tumor. For those patients whose tumors shrunk, the effect lasted for 3 to 31 months.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 shows efficacy results based on ORR and duration of response as determined by independent review according to RECIST v1.1.
Table 2. Efficacy Results, Efficacy Population
| Endpoint | AVMAPKI FAKZYNJA CO-PACK N=57 |
|---|---|
| Confirmed ORR, % (95% CI) | 44 (30.7,57.6) |
| Complete response, % | 3.5 |
| Partial response, % | 40 |
| DoR | |
| Range (months) | 3.3, 31.1 |
| Patients with DoR ≥6 months, % | 88 |
Source: AVMAPKI FAKZYNJA CO-PACK Prescribing Information
Abbreviations: CI, confidence interval; DoR, duration of response; ORR, overall response rate
Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity?
- Sex: All the patients in the trial were female, therefore only race and age differences were evaluated.
- Race: The number of patients of races other than White was limited; therefore, differences in response among races could not be determined.
- Age: Clinical studies of AVMAPKI FAKZYNJA CO-PACK did not include a sufficient number of patients aged 65 and over to determine whether they respond differently from younger patients.
- Ethnicity: The majority of patients were not Hispanic or Latino. The number of patients of other ethnicities was limited; therefore, differences in response among ethnicities could not be determined.
What are the possible side effects?
AVMAPKI FAKZYNJA CO-PACK may cause eye problems, skin problems, liver problems, and muscle problems (rhabdomyolysis).
The most common side effects of AVMAPKI FAKZYNJA CO-PACK include nausea; diarrhea; constipation; swelling in the face, legs, or arms; vomiting; acid reflux; tiredness; rash; dry or itchy skin; hair loss; infection around your fingernails or toenails; urinary tract infection; stomach-area (abdominal) pain; muscle spasms; pain in the joints; high blood pressure; blurry vision or impaired vision; dry eyes; headache; inflammation or soreness of the mouth; dry mouth; decreased appetite; loss of sense of taste; abnormal liver function tests; increase in an enzyme known as creatine phosphokinase; and decreased hemoglobin.
What are the possible side effects (results of trials used to assess safety)?
Table 3. Adverse Reactions (≥10%) in Patients With KRAS-Mutated Recurrent LGSOC Who Received AVMAPKI FAKZYNJA CO-PACK, Trial RAMP-2011
| Adverse Reaction | AVMAPKI FAKZYNJA CO-PACK, N=57 | |
|---|---|---|
| All Grades % |
Grade 3 or 47 % |
|
| Gastrointestinal disorders | ||
| Nausea | 74 | 1.8 |
| Diarrhea | 68 | 7 |
| Vomiting | 49 | 3.5 |
| Abdominal pain2 | 39 | 1.8 |
| Dyspepsia2 | 37 | 0 |
| Stomatitis2 | 35 | 3.5 |
| Constipation | 30 | 0 |
| Dry mouth | 18 | 0 |
| Decreased weight | 11 | 0 |
| General disorders and administration site condition | ||
| Fatigue2 | 72 | 3.5 |
| Edema2 | 67 | 1.8 |
| Skin and subcutaneous tissue disorders | ||
| Rash3 | 72 | 3.5 |
| Dermatitis acneiform4 | 37 | 5.3 |
| Pruritus2 | 35 | 1.8 |
| Dry skin2 | 30 | 0 |
| Alopecia2 | 23 | 0 |
| Photosensitivity2 | 16 | 0 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain2 | 68 | 1.8 |
| Joint swelling | 11 | 0 |
| Eye disorders | ||
| Vitreoretinal disorders5 | 37 | 3.5 |
| Visual impairment6 | 35 | 0 |
| Dry eye | 12 | 0 |
| Respiratory disorders | ||
| Dyspnea2 | 26 | 5.3 |
| Cough | 25 | 0 |
| Nervous system disorders | ||
| Dizziness | 23 | 1.8 |
| Headache | 16 | 0 |
| Neuropathy peripheral2 | 14 | 0 |
| Dysgeusia | 11 | 0 |
| Vascular disorders | ||
| Hemorrhage2 | 23 | 0 |
| Hypertension | 16 | 5.3 |
| Venous thromboembolism2 | 14 | 5.3 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 18 | 1.8 |
| Infections and infestations | ||
| Urinary tract infection | 25 | 3.5 |
| Paronychia | 14 | 1.8 |
| Upper respiratory tract infection | 11 | 0 |
Source: AVMAPKI FAKZYNJA CO-PACK Prescribing Information
1 Severity as defined by National Center Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
2 Includes multiple terms
3 Includes: butterfly rash, dermatitis, drug eruption, erythema, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, and rash pruritic
4 Includes: acne, dermatitis acneiform, folliculitis, perioral dermatitis, and rash pustular
5 Includes: chorioretinopathy, detachment of retinal pigment epithelium, macular fibrosis, macular hole, maculopathy, retinal detachment, retinal drusen, retinal vein occlusion, retinopathy, serous retinal detachment, serous retinopathy, subretinal fluid, vitreous detachment, and vitreous floaters
6 Includes: asthenopia, astigmatism, halo vision, metamorphopsia, photophobia, photopsia, vision blurred, visual field defect, and visual impairment
7 No Grade 4 treatment-emergent adverse events occurred
Abbreviations: LGSOC, low-grade serous ovarian cancer
Were there any differences in side effects among sex, race, and age?
- Sex: Everyone in the trial was female, therefore sex differences could not be determined.
- Race: The number of patients of races other than White was limited; therefore, differences in response among races could not be determined.
- Age: Clinical studies of AVMAPKI FAKZYNJA CO-PACK did not include a sufficient number of patients aged 65 and over to determine whether differences in safety were observed.
- Ethnicity: The majority of patients were not Hispanic or Latino. The number of patients of other ethnicities was limited; therefore, differences in safety among ethnicities could not be determined.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
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