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Response in patients with metastatic RET fusion-positive non-small cell lung cancer ( NSCLC ), advanced or metastatic RET fusion-positive thyroid cancer ( non-medullary thyroid cancer ( non-MTC )),* and advanced or metastatic RET-mutant MTC ¹

Metastatic RET Fusion-Positive NSCLC

Treatment naive ( n = 39 ) Previously treated with platinum chemotherapy ( n = 105 )

Median DoR not yet reached

( 95 % CI : 12 , NE ); median follow-up : 7.4 months ^{1 , 3}

Median DoR was 17.5 months

( 95 % CI : 12 , NE ); median follow-up : 12.1 months ^{1 , 3}

Responses in intracranial lesions were observed in

previously treated patients with measurable brain metastases ^{1 †}

CNS DoR was ≥6 months in all responders with measurable brain metastases ^{1 †} No patients received radiation therapy to the brain within 2 months prior to study entry ¹

Advanced or Metastatic RET Fusion-Positive Thyroid Cancer ( Non-MTC )

Systemic therapy naive ^‡ ( n = 8 ) Previously treated ^§ ( n = 19 )

Advanced or Metastatic RET-Mutant MTC

Cabozantinib / vandetanib treatment naive ( n = 88 )

Previously treated with cabozantinib and / or vandetanib ^|| ( n = 55 )

Find RET . Find results on Retevmo . com .

Trial Design The phase I / II , multicohort , open-label , single-arm , multicenter LIBRETTO-001 trial evaluated the efficacy of Retevmo in a population of 702 patients with metastatic RET fusion-positive NSCLC ( n = 332 ), ^¶ advanced or metastatic RET fusion-positive thyroid cancer ( non-MTC ) ^# ( n = 38 ), advanced or metastatic RET-mutant MTC ( n = 306 ), and certain other advanced solid tumors with RET alterations ( n = 26 ).** The study enrolled the following cohorts : systemic therapy-naive patients ( n = 39 ^†† ) and previously treated ( n = 105 ^††‡‡ ) patients who had progressed on platinum-based chemotherapy with metastatic RET fusion-positive NSCLC ; systemic therapy-naive ( n = 8 ^‡†† ) and previously treated ( n = 19 ^§†† ) patients with advanced or metastatic RET fusion-positive thyroid cancer ( non-MTC ); and treatment-naive ( n = 88 ^†† ) and previously treated ( n = 55 ^||†† ) patients with advanced or metastatic RET-mutant MTC . Major efficacy outcomes were ORR and DoR . In phase II , the dose for Retevmo was 160 mg PO BID . ^{1 , 4 , 5 §§}

ORR was defined as CR + PR and was assessed by independent review committee ( IRC ) according to RECIST v1.1 . ¹

All results reviewed by an IRC . ^{1 , 3}

* Primary tumor histologies included papillary thyroid cancer , poorly differentiated thyroid cancer , anaplastic thyroid cancer , and Hurthle cell thyroid cancer . ¹

†

Patients previously treated with platinum-based chemotherapy and with measurable CNS lesions at baseline according to IRC assessment . ¹

‡

Patients in this cohort received no prior systemic therapy other than radioactive iodine ( RAI ). ¹

§

Patients in this cohort received a prior systemic therapy ( including sorafenib , lenvatinib , or both ) other than RAI . ¹

||

The efficacy of Retevmo was evaluated in 55 patients with RET-mutant advanced MTC who were previously treated with cabozantinib or vandetanib enrolled into a cohort of LIBRETTO-001 . ¹

¶

Patients with advanced or metastatic RET fusion-positive NSCLC who had progressed on platinum-based chemotherapy and those without prior systemic therapy were enrolled in separate cohorts . ¹

#

Non-medullary thyroid cancers ( non-MTC ) by histology included papillary ( n = 31 ), poorly differentiated ( n = 4 ), anaplastic ( n = 2 ), and Hurthle cell ( n = 1 ). ^{1 , 4}

** Other tumors included pancreatic cancer ( n = 7 ), colon cancer ( n = 5 ), and adrenal gland carcinoma ( n = 3 ). ⁴

††

Number of patients included in the initial efficacy analysis . Efficacy was based on patients who had at least 6 months of follow-up . ¹

‡‡

Efficacy was evaluated in 105 adult patients with metastatic RET fusion-positive NSCLC who were previously treated with platinum chemotherapy enrolled into a cohort of LIBRETTO-001 . All 105 patients received systemic therapy . 58 of the 105 patients received prior anti-PD-1 / PD-L1 therapy , and 50 of the 105 patients received a prior multikinase inhibitor ( MKI ). ^{1 , 4}

§§

Patients with RET-mutant NSCLC and RET-mutant thyroid cancer ( non-MTC ) were not enrolled in the trial since RET is not the driver of tumor growth in these cancers . ^{1 , 6}

BID = twice daily ; CI = confidence interval ; CNS = central nervous system ; CR = complete response ; DoR = duration of response ; NE = not estimable ; ORR = objective response rate ; PO = orally ; PR = partial response ; RECIST = Response Evaluation Criteria in Solid Tumors .

Adverse Reactions and Laboratory Abnormalities

• The most common adverse reactions , including laboratory abnormalities , ( ≥25 %) were increased aspartate aminotransferase ( AST ), increased alanine aminotransferase ( ALT ), increased glucose , decreased leukocytes , decreased albumin , decreased calcium , dry mouth , diarrhea , increased creatinine , increased alkaline phosphatase , hypertension , fatigue , edema , decreased platelets , increased total cholesterol , rash , decreased sodium , and constipation

• Serious adverse reactions occurred in 33 % of patients who received Retevmo . The most frequent serious adverse reaction ( in ≥2 % of patients ) was pneumonia . Fatal adverse reactions occurred in 3 % of patients ; fatal adverse reactions which occurred in > 1 patient included sepsis ( n = 3 ), cardiac arrest ( n = 3 ) and respiratory failure ( n = 3 ). Permanent discontinuation due to an adverse reaction occurred in 5 % of patients who received Retevmo Adverse reactions resulting in permanent discontinuation in patients who received Retevmo included increased ALT ( 0.4 %), sepsis ( 0.4 %), increased AST ( 0.3 %), drug hypersensitivity ( 0.3 %), fatigue ( 0.3 %), and thrombocytopenia ( 0.3 %)

• Dose interruptions due to an adverse reaction occurred in 42 % of patients who received Retevmo . Adverse reactions requiring dosage interruption in ≥2 % of patients included ALT increased , AST increased , hypertension , diarrhea , pyrexia , and QT prolongation

• Dose reductions due to an adverse reaction occurred in 31 % of patients who received Retevmo . Adverse reactions requiring dosage reductions in ≥2 % of patients included ALT increased , AST increased , QT prolongation , and fatigue

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