INVICTUS: A global Phase 3 trial in ≥4th‑line GIST1

The INVICTUS study was a global, multicenter, randomized, double-blind, placebo‑controlled Phase 3 trial in 129 patients who had received ≥3 prior anticancer therapies for advanced GIST1

Invictus Trial Design1,2
INVICTUS Trial Design INVICTUS Trial Design

 

Primary endpoint1:

  • Progression-free survival, based on BICR using modified RECIST 1.1 criteria‡

Key secondary endpoint2:

  • Objective response rate based on BICR

Additional secondary endpoints2:

  • Overall survival
  • Quality of life
  • Safety
LONG-TERM FOLLOW-UP ANALYSIS
  • Follow‑up analysis (data cutoff: January 15, 2021) includes 19 months of follow‑up data after the primary analysis (data cutoff: May 31, 2019)2,3

*Patients were stratified according to prior treatments (3 vs ≥4) and ECOG PS (0 vs 1 or 2).1

†44 patients were randomized to placebo, but one did not receive treatment.

‡Lymph nodes and bone lesions were not target lesions and progressively growing new tumor nodule within a pre-existing tumor mass was progression.1

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A wide range of advanced GIST patients were enrolled in the INVICTUS trial2

The patient population of INVICTUS was the most heavily pre-treated cohort ever studied in a Phase 3, randomized, 4th‑line GIST setting.1,2

63%of patients had received 3 prior therapies
37%of patients had received ≥4 prior therapies, and some as many as 7
Selected Baseline Characteristics2 Qinlock Placebo
  (n=85) (n=44)
Median age (years) 59 65
Sex
Male(%)		 47 (55%) 26 (59%)
Race
White (%)		 64 (75%) 33 (75%)
ECOG PS (%)
ECOG PS 0 37 (44%) 17 (39%)
ECOG PS 1/2 48 (56%) 27 (61%)
Number of prior therapies (%)
3 54 (64%) 27 (61%)
≥4 (range, 4-7) 31 (36%) 17 (39%)
Primary mutation (central testing of tumor tissue) n (%)
KIT exon 9 14 (17%) 6 (14%)
KIT exon 11 47 (55%) 28 (64%)
Other KIT 2 (2%) 2 (5%)
PDGFRα 3 (4%) 0
KIT/PDGFRα wild type 7 (8%) 3 (7%)
Not available/not done§ 12 (14%) 5 (11%)

 

Patients in the INVICTUS trial were enrolled regardless of mutation.2

§Not available=tumor tissue analyzed for baseline mutations but analysis failed; Not done=biopsy completed per protocol but sample not received for analysis.2

 
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Qinlock provides powerful PFS results in advanced GIST

Qinlock demonstrated superior median PFS vs placebo in the primary analysis: 6.3 months vs 1.0 month (P<0.0001) and consistent PFS at long‑term follow‑up2,3

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Qinlock is the first and only switch‑control kinase inhibitor1,4

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The rates of Grade 3/4 adverse reactions were similar between Qinlock and placebo5

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BICR=blinded independent central review; BID=twice a day; ECOG PS=Eastern Cooperative Oncology Group Performance Status; GIST=gastrointestinal stromal tumor; KIT=KIT proto‑oncogene receptor tyrosine kinase; MOA=mechanism of action; PDGFRα=platelet‑derived growth factor receptor α; PFS=progression‑free survival; QD=once a day; RECIST=response evaluation criteria in solid tumors.

References: 1. Qinlock [package insert]. Waltham, MA: Deciphera Pharmaceuticals, Inc; 2023. 2. Blay JY, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(7):923-934. 3. von Mehren M, Heinrich M, George S, et al. Ripretinib as ≥4th‑line treatment in patients with advanced gastrointestinal stromal tumour (GIST): Long-term update from the phase 3 INVICTUS study. Poster presented at: 2021 European Society for Medical Oncology Virtual Meeting; September 16‑21, 2021. 4. Smith BD, Kaufman MD, Lu WP, et al. Ripretinib (DCC‑2618) is a switch control kinase inhibitor of a broad spectrum of oncogenic and drug‑resistant KIT and PDGFRA variants. Cancer Cell. 2019;35(5):738‑751. 5. von Mehren M, Attia S, Bauer S, et al. INVICTUS: A phase 3, interventional, double-blind, placebo-controlled study to assess the safety and efficacy of ripretinib as ≥4th line therapy in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior anticancer therapies (NCT03353753). Oral presentation at: European Society for Medical Oncology Annual Meeting; October, 2019; Barcelona, Spain.

Indication & Important Safety Info

Indication

Qinlock is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Important Safety Information

There are no contraindications for Qinlock.

Palmar‑plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1–2 PPES occurred in 21% of the 85 patients who received Qinlock. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold Qinlock and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received Qinlock with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received Qinlock. In the pooled safety population, melanoma occurred in 0.9% of patients. Perform dermatologic evaluations when initiating Qinlock and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue Qinlock at the same dose.

Hypertension: In INVICTUS, Grade 1–3 hypertension occurred in 14% of the 85 patients who received Qinlock, including Grade 3 hypertension in 7% of patients. Do not initiate Qinlock in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold Qinlock and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received Qinlock. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received Qinlock. The safety of Qinlock has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating Qinlock and during treatment, as clinically indicated. Permanently discontinue Qinlock for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: Qinlock has the potential to adversely affect wound healing. Withhold Qinlock for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Qinlock after resolution of wound healing complications has not been established.

Photosensitivity: Qinlock may cause photosensitivity reactions. In 621 patients treated with Qinlock in clinical trials, photosensitivity reactions occurred in 0.6% of patients. Advise patients to limit direct ultraviolet exposure during treatment with Qinlock and for at least 1 week after discontinuation of treatment.

Embryo‑Fetal Toxicity: Qinlock can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 1 week after the last dose. Qinlock may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of Qinlock in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong and moderate CYP3A inducers. If a moderate CYP3A inducer cannot be avoided, increase Qinlock dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during the co‑administration period. If the concomitant moderate CYP3A inducer is discontinued, resume Qinlock dosage back to 150 mg once daily 14 days after the discontinuation of the moderate CYP3A inducer.

Please see full Prescribing Information, including Patient Information.

To report SUSPECTED ADVERSE REACTIONS, contact Deciphera Pharmaceuticals, LLC, at 1-888-724-3274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indication & Important Safety Info

Indication

Qinlock is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Important Safety Information

There are no contraindications for Qinlock.

Palmar‑plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1–2 PPES occurred in 21% of the 85 patients who received Qinlock. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold Qinlock and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received Qinlock with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received Qinlock. In the pooled safety population, melanoma occurred in 0.9% of patients. Perform dermatologic evaluations when initiating Qinlock and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue Qinlock at the same dose.

Hypertension: In INVICTUS, Grade 1–3 hypertension occurred in 14% of the 85 patients who received Qinlock, including Grade 3 hypertension in 7% of patients. Do not initiate Qinlock in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold Qinlock and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received Qinlock. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients who received Qinlock and who had a baseline and at least one post‑baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received Qinlock. The safety of Qinlock has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating Qinlock and during treatment, as clinically indicated. Permanently discontinue Qinlock for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: Qinlock has the potential to adversely affect wound healing. Withhold Qinlock for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Qinlock after resolution of wound healing complications has not been established.

Photosensitivity: Qinlock may cause photosensitivity reactions. In 621 patients treated with Qinlock in clinical trials, photosensitivity reactions occurred in 0.6% of patients. Advise patients to limit direct ultraviolet exposure during treatment with Qinlock and for at least 1 week after discontinuation of treatment.

Embryo‑Fetal Toxicity: Qinlock can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 1 week after the last dose. Qinlock may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of Qinlock in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong and moderate CYP3A inducers. If a moderate CYP3A inducer cannot be avoided, increase Qinlock dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during the co‑administration period. If the concomitant moderate CYP3A inducer is discontinued, resume Qinlock dosage back to 150 mg once daily 14 days after the discontinuation of the moderate CYP3A inducer.

Please see full Prescribing Information, including Patient Information.

To report SUSPECTED ADVERSE REACTIONS, contact Deciphera Pharmaceuticals, LLC, at 1-888-724-3274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.