FDA Approves the AVMAPKI FAKZYNJA Combination Therapy as the First-Ever Treatment for Adult Patients with KRAS-mutated Recurrent Low-Grade Serous Ovarian Cancer AVMAPKI plus FAKZYNJA to be commercially available by presc

FDA Approves the AVMAPKI FAKZYNJA

Combination Therapy as the First-Ever Treatment for Adult Patients with KRAS-mutated Recurrent Low-Grade Serous Ovarian Cancer

AVMAPKI plus FAKZYNJA to be commercially available

by prescription as a convenient oral combination co-packaged together and will be known as "AVMAPKI FAKZYNJA CO-PACK"

Accelerated approval, well ahead of the June 30,

2025 PDUFA action date, was based on the Phase 2 RAMP 201 study that demonstrated a 44% overall response rate in patients with KRAS mutant

Verastem to host investor conference call and

webcast today at 2:30 pm ET

BOSTON--(BUSINESS WIRE)- May 8, 2025--Verastem Oncology

(Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, today

announced that the U.S. Food and Drug Administration (FDA) has approved AVMAPKI FAKZYNJA CO-PACK (avutometinib

capsules; defactinib tablets) for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC)

who received prior systemic therapy. AVMAPKI FAKZYNJA CO-PACK is the first and only FDA-approved medicine for this disease. This indication

is approved under accelerated approval based on the tumor response rate and duration of response. Continued approval for this indication

may be contingent upon verification and description of clinical benefit in a confirmatory trial. AVMAPKI plus FAKZYNJA is only commercially

available in the U.S. as an oral combination co-pack with the two prescription products, known as "AVMAPKI FAKZYNJA CO-PACK."

"Today's approval of AVMAPKI FAKZYNJA CO-PACK for patients

with KRAS-mutated recurrent low-grade serous ovarian cancer represents not only the first-ever FDA-approved treatment specifically for

this rare cancer but also a new day for people living with this disease who have been in desperate need of new treatment options,"

said Dan Paterson, president and chief executive officer of Verastem Oncology. "We are very proud to bring two innovative medicines

in one combination treatment to the LGSOC community. We thank the researchers, patients, and their families participating in our clinical

trials, the patient advocacy community, the FDA, and everyone at Verastem for their dedication and commitment to helping us bring AVMAPKI

FAKZYNJA CO-PACK to patients in the U.S."

The accelerated approval of AVMAPKI FAKZYNJA CO-PACK is based on the

Phase 2 RAMP 201 clinical trial, which evaluated the combination of AVMAPKI and FAKZYNJA in adult patients with measurable KRAS-mutated

"Low-grade serous ovarian cancer is a rare and highly recurrent

cancer with limited effective treatment options. This first-ever FDA approval in this disease was based on the primary analysis of the

Phase 2 RAMP 201 trial, in which the combination of avutometinib and defactinib resulted in a significant overall response rate for patients

with a KRAS mutation while being generally well tolerated," said Rachel Grisham, M.D., Section Head, Ovarian Cancer at Memorial

Sloan Kettering Cancer Center in New York, NY and Global Lead Principal Investigator of GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301. "The

approval of avutometinib plus defactinib brings a much-needed therapeutic option to patients and establishes this combination as the new

standard of care for women with recurrent low-grade serous ovarian cancer harboring a KRAS mutation. I look forward to progressing the

confirmatory Phase 3 trial, RAMP 301, where we look to continue to support the ongoing body of research of this combination in women with

and without a KRAS mutation."

"To see our early research in both the FRAME and RAMP 201 trial

in recurrent low-grade serous ovarian cancer advance the combination of avutometinib and defactinib to now be the first-ever FDA-approved

therapy for this disease is what gives us real hope when treating patients with rare or difficult-to-treat gynecological cancers,"

said Professor Susana Banerjee, M.B.B.S., M.A., Ph.D., F.R.C.P, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust

and Team Leader in Women's Cancers at The Institute of Cancer Research, London and Global Lead Principal Investigator of ENGOTov60/GOG3052

/NCRI/RAMP201. "With this approval, we thank all of the patients and researchers who participated in this trial, and the low-grade

serous ovarian cancer community for their contributions to help bring the first FDA-approved treatment for KRAS-mutated recurrent LSGOC

and changing the treatment possibilities for RAS/MAPK-pathway-driven cancers. We now need to build on this milestone to bring this new

treatment to patients around the world."

Prior to this approval, there were no FDA-approved treatments specifically

for KRAS-mutated recurrent LGSOC, a rare and distinct ovarian cancer that differs from high-grade serous ovarian cancer in both its biology

and how it responds to treatment.

"One of the most devastating aspects of my LGSOC diagnosis was

learning there are no FDA-approved treatments for this rare cancer. While there were some treatment options at the time that I could try, I

made it my mission to advocate for research specific to my disease," said Nicole Andrews, chair of the STAAR Low-Grade Serous Ovarian

Cancer Foundation. "Today we're celebrating a milestone with the first-ever FDA-approved treatment option specifically for patients

with recurrent LGSOC with a KRAS mutation. The low-grade serous ovarian cancer community is hopeful and excited about the potential benefits

of this treatment and the progress toward improving the diagnosis, awareness, and research for LGSOC."

AVMAPKI FAKZYNJA CO-PACK is the first treatment to receive regulatory

approval anywhere in the world, specifically for KRAS-mutated recurrent LGSOC. The Company believes AVMAPKI FAKZYNJA CO-PACK is also the

first-ever oral, novel/novel combination therapy approved in oncology. Verastem initiated a rolling new drug application (NDA) with

the FDA in May 2024 and completed its NDA submission in October 2024. The FDA granted Priority Review, and the

approval was received in advance of its Prescription Drug User Fee Act (PDUFA) action date of June 30, 2025. The FDA granted Breakthrough

Therapy Designation for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based

chemotherapy, in May 2021. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by

the FDA for the treatment of LGSOC.

The AVMAPKI FAKZYNJA CO-PACK is expected to be available for adult

patients with KRAS-mutated recurrent LGSOC in the U.S. in one week.

Verastem's Commitment to Patient Support

Verastem Oncology is committed to providing patient access and reimbursement

support through its Verastem Cares program in the U.S. Verastem Cares offers a range of patient access and reimbursement

support services to help U.S. patients prescribed AVMAPKI FAKZYNJA CO-PACK receive treatment access. Verastem Cares case managers

can be reached at 1-866-351-8372 between 8:00 am-8:00 pm Eastern Time, Monday through Friday.

Verastem to Host Investor Call on AVMAPKI FAKZYNJA CO-PACK FDA

Verastem will hold an investor conference call and webcast today

at 2:30 pm ET, to discuss the FDA approval of AVMAPKI FAKZYNJA CO-PACK. To access the conference call, please dial (844) 763-8274 (local)

or (412) 717-9224 (international) at least 10 minutes prior to the start time and ask to be joined into the Verastem Oncology conference

call. A live audio webcast of the call, along with accompanying slides, will be accessible under "Events & Presentations"

in the Investors & Media section of the Company's website at www.verastem.com.

Basis of Approval: RAMP 201 Trial Results

The efficacy of AVMAPKI and FAKZYNJA, in combination, was evaluated

in the RAMP 201 clinical trial (NCT04625270), an open-label, multicenter study that included 57 adult patients with measurable KRAS-mutated

recurrent LGSOC. Patients were required to have received at least one prior systemic therapy, including a platinum-based drug. Patients

received AVMAPKI 3.2 mg orally twice weekly for the first three weeks out of a four-week cycle and FAKZYNJA 200 mg orally twice daily

for the first three weeks out of a four-week cycle until disease progression or unacceptable toxicity. The major efficacy outcome measure

was overall response rate (ORR) assessed by blinded independent review committee (BIRC) 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 eight weeks for the first 72 weeks and every 12 weeks thereafter.

In the study, AVMAPKI and FAKZYNJA, in combination, showed in patients

with a KRAS mutation a confirmed ORR by BICR of 44% (25/57; 95% CI: 31-58). The median DOR ranged from 3.3 to 31.1 months in the KRAS

The safety of AVMAPKI and FAKZYNJA, in combination, was evaluated in

57 patients with KRAS-mutated recurrent LGSOC. Possible serious side effects with AVMAPKI FAKZYNJA CO-PACK include ocular disorders,

skin toxicities (rash), hepatotoxicity, rhabdomyolysis, and fetal harm when administered during pregnancy. The most common side effects,

including laboratory changes, of AVMAPKI FAKZYNJA CO-PACK include increased levels of an enzyme in the blood (CPK), nausea, fatigue, abnormal

liver test (AST), and rash.

About Low-Grade Serous Ovarian Cancer (LGSOC)

LGSOC is a rare ovarian cancer that is insidious and persistent. LGSOC

is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and

less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and 80,000 worldwide are living

with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival

of approximately ten years. Approximately 70 percent of LGSOC shows RAS pathway-associated mutations, and 30 percent of people with LGSOC

have a KRAS mutation. The majority of patients report a negative impact of LGSOC on their mental and physical health, fertility, and long-term

quality of life. The current standard of care for LGSOC includes hormone therapy and chemotherapy.

About AVMAPKI and FAKZYNJA Combination Therapy

AVMAPKI (avutometinib) inhibits MEK kinase activity while also blocking

the compensatory reactivation of MEK by upstream RAF. RAF and MEK proteins are regulators of the RAS/RAF/MEK/ERK (MAPK) pathway.